Journal Of Cancer Research And Clinical Oncology[JOURNAL]
Sun
200 papers
Computational identification of cross-reactive TCR epitopes with ARDitox.
Murcia Pienkowski V, Boschert T, Skoczylas P … +9 more , Sanecka-Duin A, Jasiński M, Król-Józaga B, Mazzocco G, Stachura S, Bunse L, Kaczmarczyk J, Green EW, Blum A
J Cancer Res Clin Oncol · 2025 Nov · PMID 41175267 · Full text
BACKGROUND: Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T cell receptors (TCRs), have demonstrated therapeutic efficacy. However, some engineered high-affinity TCRs hav...
BACKGROUND: Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T cell receptors (TCRs), have demonstrated therapeutic efficacy. However, some engineered high-affinity TCRs have caused fatal off-target immunotoxicity due to targeting epitopes later found to be expressed by both tumor cells and healthy tissues. Unfortunately, TCRs can be cross-reactive to epitopes with highly distinct sequences, making prediction difficult, and the exquisite sequence specificity of TCRs means that safety studies in mice miss human-specific epitopes. METHODS: To address this issue, we developed ARDitox, a novel in silico method based on computational immunology and artificial intelligence (AI) for predicting and analyzing potential TCR off-target toxicities. We tested the performance of ARDitox on four TCRs reported to target tumor-associated antigens, two of which are known to cause clinical immunotoxicity (MAGEA3 and MAGEA3 epitopes), one of which has experimentally identified off-target antigens (AFP epitope), and the last one for which no cross-reactive epitopes are known (NY-ESO-1). RESULTS: ARDitox confirmed the previously identified immunotoxic epitopes. We then expanded our analyses to a novel TCR targeting the tumor-associated antigen NLGN4X, frequently upregulated in gliomas. For this target, ARDitox identified a cross-reactive peptide that would not have been found using mouse models, highlighting the value of our computational approach. CONCLUSIONS: Our findings underscore the value of the ARDitox in silico method for the early and reliable identification of off-target epitopes for further preclinical evaluation. This platform strongly supports the development of safer TCR-mediated immunotherapies.
Distinct immunologic kinetics and cytomegalovirus reactivation incidence with rituximab- versus obinutuzumab-bendamustine in follicular lymphoma: a single-center case series study.
D'Addona M, Pezzullo L, Settembre L … +11 more , Vaccaro E, Guariglia R, Serio B, Mettivier L, Gigantiello A, Signorile G, Bertolini A, Picone F, Cuffa B, Giudice V, Selleri C
J Cancer Res Clin Oncol · 2025 Nov · PMID 41175237 · Full text
Rituximab and obinutuzumab, anti-CD20 monoclonal antibodies, are widely employed for treatment of follicular lymphoma (FL) by targeting both neoplastic and normal CD20-expressing B lymphocytes, consequently inducing immu...
Rituximab and obinutuzumab, anti-CD20 monoclonal antibodies, are widely employed for treatment of follicular lymphoma (FL) by targeting both neoplastic and normal CD20-expressing B lymphocytes, consequently inducing immunosuppression. In this condition, viral reactivations are common and represent a major cause of morbidity and mortality. In this single-center two-arm observational real-life study, we evaluated incidence, immunological and serological status, and clinical outcomes of cytomegalovirus (CMV) reactivation in FL patients treated with bendamustine + rituximab (R-BENDA; N = 23) or obinutuzumab (G-BENDA; N = 23). CMV reactivation more frequently occurred in patients treated with R-BENDA compared to G-BENDA (P = 0.022), and immune kinetics showed significant differences between the two groups, with a deeper and earlier immunosuppression in R-BENDA treated subjects. Moreover, R-BENDA group displayed a significant higher risk of CMV reactivation compared to G-BENDA (hazard ratio, 2.232; 95% confidence interval 1.107-4.500; P = 0.0249). However, G-BENDA patients tended to have a shorter 5-year overall survival (59% vs. 86.7%, G-BENDA vs. R-BENDA; P = 0.0903). By multivariate analysis, B symptoms were an independent predictor of CMV reactivation, and high baseline SUV as an additional risk factor in R-BENDA patients. In conclusion, anti-CD20 agent could increase the risk of CMV reactivation in FL patients, especially in R-BENDA treated subjects who experienced early and deep immunosuppression. Therefore, close monitoring of clinical and laboratory data may improve outcomes in FL patients by preventing CMV disease, especially in those treated with rituximab who are more prone to viral reactivation. However, larger prospective studies are required to confirm our preliminary results.
Immune checkpoint inhibition alters patterns of failure in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy.
Taugner J, Stamer S, Hofstetter K … +9 more , Eze C, Käsmann L, Clasen K, Hartig P, Spengler W, Groß T, Manapov F, Belka C, Niyazi M
J Cancer Res Clin Oncol · 2025 Nov · PMID 41175229 · Full text
PURPOSE: We compared failure patterns in patients with inoperable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) alone versus CRT combined with sequential and/or concurrent immune check...
PURPOSE: We compared failure patterns in patients with inoperable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) alone versus CRT combined with sequential and/or concurrent immune checkpoint inhibitors (CRT-IO). METHODS: Retrospective real-world data from 221 patients across two German tertiary cancer centers were analyzed. Of these, 74 received CRT-IO, including sequential durvalumab (85%) and concurrent/sequential nivolumab (15%), while 148 received CRT alone. First failure site and time to failure were compared. RESULTS: Between 2012 and 2022, all patients received thoracic radiotherapy (≥ 60 Gy) and at least two cycles of platinum-based chemotherapy. Induction chemotherapy was administered in 36%, and induction chemo-immunotherapy in 2%. Median follow-up was 51.7 months (95% CI 47.0-56.4). Median overall survival (OS) for the entire cohort was 37.1 months (95% CI 26.0-48.2), with OS in the CRT-IO group not reached vs. 27.1 months (95% CI 18.5-25.7) in the CRT group (p < 0.001). Median progression-free survival (PFS) was 22.8 months (95% CI 6.4-39.1) for CRT-IO versus. 9.9 months (95% CI 7.0-12.8) for CRT (p = 0.001, see Fig. 1). Failure patterns differed significantly. CRT-IO patients had lower loco-regional progression (LRP) rates (9.5% vs. 21.8%, p = 0.023) and were more frequently alive without progression (45.9% vs. 16.3%, p < 0.001). Brain metastasis (BM) as the first failure, multifocal progression (MFP) and isolated extracranial distant metastasis (ecDM) rates were comparable between the CRT and CRT-IO subgroup. Women had a higher risk of isolated BM (17.3% vs. 6.8%, p = 0.016), whereas squamous cell carcinoma (SCC) patients had higher LRP rates (25.3% vs. 13.0%, p = 0.016). Median post-progression survival (PPS) was 19.4 months (95% CI 16.8-22.0) for CRT-IO and 9.5 months (95% CI 5.8-13.1) for CRT (p = 0.207). PPS was longer after BM (19.9 months) vs. LRP (8.5 months, p = 0.076) and significantly better in women (20.7 vs. 8.9 months, p = 0.012) and adenocarcinoma/non-otherwise-specified-carcinoma (AC/NOS) vs. SCC (p < 0.001). CONCLUSION: CRT-IO significantly improves OS, PFS, and LRP control compared to CRT alone. Failure patterns and survival disparities by histology and gender suggest tailored surveillance and treatment strategies are needed. Further studies should optimize management of LRP and long-term outcomes in CRT-IO-treated patients.
Immunotherapy with and without radiotherapy following the diagnosis of bone metastasis for stage IV non-small cell carcinoma.
Beyon J, Collins JE, Welch CA … +1 more , Kamran A
J Cancer Res Clin Oncol · 2025 Oct · PMID 41165912 · Full text
INTRODUCTION: This retrospective study compared the impact of radiotherapy (RT) and immunotherapy (IO) on survival in patients with stage IV non-small cell lung cancer (NSCLC) following a diagnosis of bone metastasis. ME...
INTRODUCTION: This retrospective study compared the impact of radiotherapy (RT) and immunotherapy (IO) on survival in patients with stage IV non-small cell lung cancer (NSCLC) following a diagnosis of bone metastasis. METHODS: The TriNetX database (2013-2024) was queried for adults (≥ 18 years) with NSCLC who received IO after diagnosis of bone metastases. Patients were then divided into cohorts based on whether they also received RT after bone metastasis diagnosis. RESULTS: A risk assessment revealed RT + IO was associated with significantly improved survival at 3 months (92% vs. 86% alive, p < 0.001), 6 months (79% vs. 72%, p = 0.002), and 1 year (59% vs. 54%, p = 0.014). In patients with adenocarcinoma, RT + IO was associated with improved survival at 3 months (92% vs. 88%, p = 0.046) but not at 6 months or 1 year. Similarly, in patients with squamous cell carcinoma, IO + RT was also associated with higher survival (94% vs. 85%, p = 0.040) at 3 months but not at 6 months or 1 year. A Cox proportional hazards model found significant lower hazard of death in the RT + IO group (hazard ratio [HR] = 0.83) and several covariates were associated with higher hazard, including adrenal metastasis (HR = 1.7), liver metastasis (HR = 1.4), lymph node metastasis (HR = 1.3), hypoalbuminemia (< 3.45 g/dL; HR = 1.5), and inpatient or observation care (HR = 1.4). DISCUSSION: This study highlights the potential importance of combining RT with IO, particularly in the early period after bone metastasis diagnosis.
Shared decision-making in cancer care in Bangladesh: evidence from a resource-constrained setting.
Shahjalal M, Doshi RH, Garg SK … +2 more , Cartmell KB, Dee EC
J Cancer Res Clin Oncol · 2025 Oct · PMID 41165863 · Full text
BACKGROUND: Shared decision-making (SDM) is a key component of patient-centered cancer care; however, its implementation remains poorly understood in resource-limited settings like Bangladesh. The purpose of this survey...
BACKGROUND: Shared decision-making (SDM) is a key component of patient-centered cancer care; however, its implementation remains poorly understood in resource-limited settings like Bangladesh. The purpose of this survey is to assess the prevalence of SDM, identify its associated factors, and evaluate its impact on patient satisfaction within this context. METHODS: We conducted a cross-sectional survey using convenience sampling between May and July 2024 at a tertiary care specialized cancer hospital in Bangladesh. Eligible participants were adult patients with cancer who had received at least two cycles of chemotherapy or radiation therapy and had the physical and decisional capacity to participate. Chi-square tests assessed bivariate associations, and multivariable logistic regression, adjusted for age, education, and treatment modality, identified independent predictors of SDM participation. RESULTS: Among 231 participants (mean [SD] age, 51.6 [13.2] years), 55% were women and 91% were not in formal employment. Overall, 32% of patients reported participating in SDM, whereas 59% expressed a preference for it. Patients with no formal education had 85% lower odds of participating in SDM compared to those with schooling (adjusted odds ratio [AOR], 0.15; 95% confidence interval [CI] 0.06–0.38; P < 0.001). Compared to the youngest group, middle-aged patients had 89% lower odds of participating in SDM (AOR, 0.11; 95% CI 0.04–0.31; P < 0.001), and older patients had 95% lower odds (AOR, 0.05; 95% CI 0.01–0.18; P < 0.001). Working patients had over four times the odds of engaging in SDM compared to non-working patients (AOR, 4.24; 95% CI 2.25–10.17; P = 0.001). Actual involvement in SDM, desire for additional information, and preferred decision-making role were significantly associated with satisfaction (P < 0.001 for all). CONCLUSIONS: The significant disconnect between patients' high preference for and low participation in SDM highlights a critical gap in patient-centered oncology care in Bangladesh. Systemic barriers, such as severe time constraints and low health literacy, must be addressed through targeted interventions, including clinician training and the development of low-literacy decision aids, to advance equitable cancer care.
Outcomes of conversion surgery following chemotherapy for initially unresectable metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study in Taiwan.
Su PJ, Lu WH, Liao TK … +3 more , Wang CJ, Chao YJ, Shan YS
J Cancer Res Clin Oncol · 2025 Oct · PMID 41165833 · Full text
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a high mortality rate. For patients with metastatic PDAC (mPDAC) initially deemed unresectable, systemic chemotherapy followed by conversion s...
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a high mortality rate. For patients with metastatic PDAC (mPDAC) initially deemed unresectable, systemic chemotherapy followed by conversion surgery may offer an improvement in survival. This study aimed to compare survival between mPDAC patients undergoing conversion surgery versus chemotherapy alone, and identify factors associated with recurrence following conversion surgery. METHODS: We conducted a retrospective cohort study of patients with mPDAC treated with systemic chemotherapy at National Cheng Kung University Hospital, Taiwan, between September 2020 and January 2023. Patients who subsequently underwent conversion surgery were analyzed to identify factors associated with recurrence. Clinicopathologic, treatment, and surgical variables were extracted from medical records. Recurrence-free survival (RFS) was defined from the date of conversion surgery to recurrence or death. Survival outcomes were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards regression with stepwise selection was applied to identify independent predictors of recurrence. RESULTS: Among 151 patients who underwent chemotherapy, 33 subsequently received conversion surgery. In the patients who received conversion surgery, male sex (HR 4.33, 95% CI 1.60-11.72), tumor location in the head/uncinate process (HR 2.79, 95% CI 1.03-7.58), and regression grade 2 (HR 4.65, 95% CI 1.41-15.30) were significantly associated with worse RFS. CONCLUSION: Among patients with mPDAC who underwent conversion surgery after chemotherapy, several factors were independently associated with shorter RFS, including male sex, tumor location in the pancreatic head/uncinate process, and histologic regression grade 2.
Prognostic impact of central nervous system prophylaxis and a simplified BL model in primary testicular lymphoma: a real-world multicenter study.
Liu S, Yang P, Zhao Y … +6 more , Zhou S, Luo H, Cen X, Dong F, Wan W, Jing H
J Cancer Res Clin Oncol · 2025 Oct · PMID 41162780 · Full text
PURPOSE: Primary testicular lymphoma (PTL) is a rare but aggressive form of extranodal lymphoma with a high risk of central nervous system (CNS) relapse and poor long-term survival. However, the optimal CNS prophylaxis s...
PURPOSE: Primary testicular lymphoma (PTL) is a rare but aggressive form of extranodal lymphoma with a high risk of central nervous system (CNS) relapse and poor long-term survival. However, the optimal CNS prophylaxis strategy and effective prognostic models for PTL remain unclear. This study aimed to evaluate the prognostic impact of intrathecal (IT) prophylaxis and to develop a novel, simplified prognostic model in a Chinese multicenter cohort. METHODS: We retrospectively collected data from a total of 55 patients with PTL, treated at three major tertiary hospitals in China. Multivariate Cox regression identified independent prognostic factors for overall survival (OS) and progression-free survival (PFS). A new risk stratification model (BL model, based on B symptoms and LDH levels) was constructed and validated using time-dependent C-index and calibration plots, and compared with the International Prognostic Index (IPI). RESULTS: IT prophylaxis reduced CNS relapse rates (9.1% vs. 36.4%, p < 0.001) and was independently associated with improved OS (HR = 0.18, p < 0.001) and PFS (HR = 0.21, p < 0.001). The BL model (B symptoms and LDH), demonstrated superior predictive accuracy compared to the IPI, with higher AUCs at 1-, 3-, and 5-year OS (0.883, 0.894, 0.854 vs. 0.656, 0.804, 0.724), and a corrected C-index of 0.798. Calibration analysis confirmed good agreement between predicted and observed survival. CONCLUSION: IT prophylaxis significantly improves survival and reduces CNS relapse in PTL. The BL model provides a simple yet effective tool for individualized risk stratification, outperforming IPI and aiding clinical decision-making in PTL.
Cost-effectiveness analysis of pembrolizumab versus chemotherapy in advanced non-small cell lung cancer in China based on real-world studies.
Wan N, Yang C, Wang B … +13 more , Guo Y, He Z, Lv Y, Lu L, Yang N, Xiao W, Chen Y, Yuan J, Yang D, Liu T, Fang W, Chen Z, Liang W
J Cancer Res Clin Oncol · 2025 Oct · PMID 41152654 · Full text
BACKGROUND: Although pembrolizumab has been shown to be effective, its high price has prevented it from being widely used. Especially in the real world, the application situation is still uncertain. The purpose of this s...
BACKGROUND: Although pembrolizumab has been shown to be effective, its high price has prevented it from being widely used. Especially in the real world, the application situation is still uncertain. The purpose of this study was to evaluate the cost-effectiveness of pembrolizumab on the basis of real-world studies, from the perspective of the health care system. METHODS: Retrospectively, 630 patients with advanced NSCLC treated with pembrolizumab (monotherapy or combination chemotherapy) versus chemotherapy alone from January 2020 to December 2022 at a large 3 A hospital in China were included. Confounders between groups were eliminated using propensity score matching analysis. A partitioned survival model was developed to evaluate the cost-effectiveness of pembrolizumab versus chemotherapy for the treatment of advanced NSCLC based on progression-free survival, overall survival, and the incidence of adverse effects in the two matched groups (n = 450 patients). The incremental cost-effectiveness ratio was calculated. The impact of a drug donation program on the cost-effectiveness of pembrolizumab was also evaluated. RESULTS: Pembrolizumab significantly improved median PFS in patients (15.5 months vs. 8.8 months). The median OS in the Pembrolizumab group has not been reached, while it was 26.2 months in the chemotherapy group. When the drug donation program is not considered, the ICER of pembrolizumab is $146,409.07/QALY. Regardless of whether the willingness-to-pay threshold is set at three times the per capita GDP of China ($36,070.2) or three times the per capita GDP of Guangdong Province ($64,523.8), the use of pembrolizumab is not cost-effective. However, after considering the drug donation program, the ICER decreased to $56,127.74/QALY. Under the willingness-to-pay threshold of three times the per capita GDP of Guangzhou in 2022 ($64,523.8), pembrolizumab became a cost-effective choice. CONCLUSION: In the treatment of advanced NSCLC in China, pembrolizumab, particularly when considering the drug donation program, offers better survival outcomes and becomes cost-effective. This highlights the importance of such programs in making high-cost treatments accessible in real-world clinical settings.
Intrahepatic cholangiocarcinoma as a unique subtype: key updates from current guidelines.
Schindler A, Denecke T, Seehofer D … +2 more , van Bömmel F, Berg T
J Cancer Res Clin Oncol · 2025 Oct · PMID 41137969 · Full text
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Quality of life following total neoadjuvant therapy for rectal cancer.
Wurschi GW, Diefenhardt M, Kaufmann J … +13 more , Ha HM, Schneider M, von Ohlen DS, Schöneich M, Cieslak A, Depardon A, Becker JN, Rühle A, Ehret F, Römer M, Rißner F, Hinz A, Pietschmann K
J Cancer Res Clin Oncol · 2025 Oct · PMID 41137944 · Full text
PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT), comparing outcomes with the German general...
PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT), comparing outcomes with the German general population and colorectal cancer (CRC) patients treated with curative intent. METHODS: In a multicenter, cross-sectional study within the "TNTox" study framework (DRKS 00033000), EORTC QLQ-C30 and QLQ-CR29 questionnaires were distributed to LARC patients who had completed TNT. Mean reference values were compared descriptively, and further exploratory comparisons based on clinical features were performed. RESULTS: The study included responses from 72 patients. Compared to the German general population, a reduction in mean HRQoL across most domains was observed; the strongest effect was observed for role functioning (- 28.7 points, Cohen's d = - 0.95), social functioning (- 25.3 points, d = - 0.89), and for diarrhea (+ 9.9 points, d = 0.80). General HRQoL was similar to that of CRC patients following curative treatment. However, some symptom scores, notably fecal incontinence (+ 13.4 points, d = 0.52), impotence (+ 29.0 points, d = 0.73), and dyspareunia (+ 10.4 points, d = 0.40) appeared to be higher. Significant factors associated with HRQoL included the presence of chronic treatment-related toxicity and duration of TNT; no major differences were observed between patients with or without NOM or stoma. CONCLUSION: LARC patients undergoing TNT showed comparable HRQoL outcomes to CRC patients treated with curative intent, but with reductions when compared to the general population. The presence of chronic toxicity significantly impacts HRQoL. Survivors may experience HRQoL impairments post-TNT, underscoring the necessity for ongoing management of chronic toxicity tailored to their needs.
CGREF1 promotes cancer cell migration and predicts poor prognosis in colorectal cancer.
Liu M, Yang H, Zhang D … +1 more , Chen J
J Cancer Res Clin Oncol · 2025 Oct · PMID 41125935 · Full text
PURPOSE: Cell growth regulator with EF-hand domain 1 (CGREF1) has been implicated in the upregulation across various cancer types. However, its functional role and clinical relevance in colorectal cancer (CRC) remain poo...
PURPOSE: Cell growth regulator with EF-hand domain 1 (CGREF1) has been implicated in the upregulation across various cancer types. However, its functional role and clinical relevance in colorectal cancer (CRC) remain poorly characterized. The current study explored the role of CGREF1 in the development and progression CRC. METHODS: Bioinformatics analysis was used to examine the expression of CGREF1 in various malignancies, including CRC. Immunohistochemistry (IHC) and Quantitative real-time PCR (qRT-PCR) were performed to determine the expression of CGREF1 in CRC tissues. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of CGREF1 on the development and progression of CRC. RESULTS: Bioinformatics analyses confirmed significant upregulation of CGREF1 in multiple malignancies, including CRC. qRT-PCR validated these findings by showing a marked increase in CGREF1 mRNA levels in CRC tissues relative to paired normal adjacent tissues. Consistently, IHC evaluations further corroborated these findings, demonstrating that CGREF1 expression was significantly upregulated in human CRC tissues compared to matched adjacent normal intestinal epithelial tissues. Notably, high expression levels of CGREF1 were significantly correlated with aggressive tumor characteristics and poorer prognostic outcomes in CRC patients. Specifically, CGREF1 expression was markedly elevated in high-grade budding (Bd3), highlighting its potential role in this critical process. Knockdown of CGREF1 in CRC cells significantly attenuated the migration capacity in vitro and in vivo, but did not affect cellular proliferation. Furthermore, knockdown of CGREF1 decreased attenuated F-actin polymerization and reduced pseudopodia formation in CRC cells. CONCLUSION: Our findings establish CGREF1 as a critical promoter of CRC migration and a potential prognostic biomarker, providing novel insights into the molecular mechanisms underlying CRC metastasis.
Response to PD-1 inhibition in MMRd/MSS pancreatic ductal adenocarcinoma: the relevance of parallel testing.
Pahl HL, Lassmann S, Schultheis AM … +7 more , Rau S, Börries M, Duyster J, Zaiss M, Quante M, Becker H, MTB-FR Network
J Cancer Res Clin Oncol · 2025 Oct · PMID 41120797 · Full text
While pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, a small fraction of patients show high microsatellite instability (MSI-H) and may respond to immune checkpoint inhibition. An MSI-H genotype is usua...
While pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, a small fraction of patients show high microsatellite instability (MSI-H) and may respond to immune checkpoint inhibition. An MSI-H genotype is usually associated with deficiencies in the DNA mismatch-repair mechanism (MMRd). However, discordances between the mismatch-repair status by immunohistochemistry and the microsatellite status by molecular analyses have been noted. To date it is not clear whether PDAC patients with mutations in mismatch repair genes, which result in loss of protein expression (MMRd), who nonetheless retain microsatellite stability (MSS), can profit from checkpoint inhibitor therapy. Here, we present the case of a PDAC patient, diagnosed as MMRd/MSS, who responded to checkpoint inhibitor therapy after failing two lines of chemotherapy. Our data suggest that both MMR and microsatellite status should be determined in PDAC patients and that MMRd status alone, even in an MSS phenotype, can constitute an indication for checkpoint inhibitor therapy.
Cancer incidence trends in Baden-Württemberg (Southwest Germany) during and after the COVID-19 pandemic (2020-2023).
Jansen L, Hermann S, Bergbold S … +1 more , Arndt V
J Cancer Res Clin Oncol · 2025 Oct · PMID 41117991 · Full text
PURPOSE: While several countries reported an impact of the coronavirus disease (COVID-19) pandemic on cancer incidence in 2020, little is known about trends in the following years. This study examined changes in cancer i...
PURPOSE: While several countries reported an impact of the coronavirus disease (COVID-19) pandemic on cancer incidence in 2020, little is known about trends in the following years. This study examined changes in cancer incidence in Baden-Württemberg between 2015 and 2023. METHODS: Data from the Baden-Württemberg Cancer Registry were used to calculate age-standardized and age-specific incidence rates for all cancers combined and for colorectal, lung, prostate, and breast cancer. Incidence rates for 2020 to 2023 were compared with those from a pre-pandemic reference period (2017-2019) and with expected rates based on modeled trends between 2015 and 2019 using standardized incidence ratios (SIRs). RESULTS: Among men, the age-standardized overall cancer incidence declined significantly from 734.0 per 100,000 in 2019 to 672.9-681.7 during 2020-2023. In women, incidence declined from 542.2 in 2019 to 504.3-524.4, with statistically significant reductions in 2022 and 2023. Compared to 2017-2019 levels, 14,214 fewer cases (-5.5%) were diagnosed in 2020-2023; relative to model-based expectations, 19,525 fewer cases (-7.6%) were reported. Site-specific analyses showed significantly lower colorectal cancer incidence in both sexes from 2020 onwards (SIRs: 0.81-0.90). For men, part of this decline may reflect a pre-existing downward trend. No significant deviations were found for lung and prostate cancer. Female breast cancer incidence was significantly lower only in 2020 (SIR: 0.93). CONCLUSION: Cancer incidence in Baden-Württemberg remained consistently below pre-pandemic and expected levels from 2020 through 2023. Further research is warranted to disentangle potential contributing factors, including post-pandemic effects, competing mortality risks, and migration-related population changes.
E3 ubiquitin ligase BTRC inhibits the proliferation and tumor growth of glioma cells through the NFAT5/AQP4 axis.
Li Y, Tang S, Jiang K … +2 more , Deng P, Hu X
J Cancer Res Clin Oncol · 2025 Oct · PMID 41117947 · Full text
OBJECTIVE: Ubiquitination is integral to the pathogenesis of various tumors. This study sought to elucidate the role and underlying mechanisms of BTRC-mediated ubiquitination and degradation in glioma. METHOD: The expres...
OBJECTIVE: Ubiquitination is integral to the pathogenesis of various tumors. This study sought to elucidate the role and underlying mechanisms of BTRC-mediated ubiquitination and degradation in glioma. METHOD: The expression levels of beta-transduced in repeat containing E3 ubiquitin protein ligase (BTRC), nuclear factor of activated T cells 5 (NFAT5) and aquaporin-4 (AQP4) were assessed by RT-qPCR/Western blot. The association and underlying mechanisms of BTRC, NFAT5, and AQP4 were examined through co-immunoprecipitation, cycloheximide chase, and chromatin immunoprecipitation assays. The influence of the BTRC/NFAT5/AQP4 axis on the malignant biological functions of glioma cells and tumor growth was evaluated through a series of in vitro and in vivo experiments. RESULTS: In glioma cells, BTRC expression was observed to be downregulated. Overexpression of BTRC inhibits proliferation, migration and invasion, while promoting apoptosis in glioma cells. Mechanically, BTRC overexpression facilitates ubiquitination and degradation of NFAT5, thereby inhibiting NFAT5-mediated transcriptional activation of AQP4. Functional recovery assays demonstrated that the overexpression of either AQP4 or NFAT5 counteracted the intervention effect of upregulation of BTRC on the malignant behavior of glioma cells. In vivo animal experiments further confirmed the results of the in vitro experiments, indicating that the overexpression of BTRC inhibits tumor growth through the NFAT5/AQP4 axis. CONCLUSION: BTRC negatively modulates the transcription of AQP4 via NFAT5 in glioma cells, thereby influencing their malignant biological functions and tumor growth.
Retraction Note: Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer.
Chan D, Zheng Y, Tyner JW … +6 more , Chng WJ, Chien WW, Gery S, Leong G, Braunstein GD, Phillip Koeffler H
J Cancer Res Clin Oncol · 2025 Oct · PMID 41117828 · Full text
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Molecular detection of HPV, EBV, and polyomaviruses in thyroid tumors and their clinicopathological relevance.
Ramadan N, Rabiee OA, Hafez MM … +4 more , Fattah NFA, Khorshed EN, Khalafalla K, Nassar A
J Cancer Res Clin Oncol · 2025 Oct · PMID 41115984 · Full text
OBJECTIVE: Oncogenic viruses have been implicated in thyroid carcinogenesis, yet their prevalence and clinicopathological associations remain incompletely understood. Thus, it is crucial to investigate the prevalence of...
OBJECTIVE: Oncogenic viruses have been implicated in thyroid carcinogenesis, yet their prevalence and clinicopathological associations remain incompletely understood. Thus, it is crucial to investigate the prevalence of human papillomavirus (HPV), Epstein-Barr virus (EBV), and polyomaviruses (JCV and BKV) in thyroid tumors and assess their association with clinic-pathological characteristics. METHODS: This study included 70 fresh biopsy samples collected from 45 TC patients and 25 patients with benign thyroid tumors, along with 10 normal thyroid tissues. Viral DNA was extracted and screened for HPV, EBV, and polyomaviruses using SYBR Green-based real-time PCR. RESULTS: HPV, EBV, and polyomaviruses, particularly JCV, were detected at significantly lower frequencies in the normal group when compared to malignant and benign groups (p-value = 0.030, p-value = 0.030, and p-value = 0.001, respectively). In TC patients, HPV common, HPV-16, HPV-6, and HPV-11 positivity was correlated with obesity (p-value < 0.05), polyomaviruses, particularly JCV, with older age (p-value = 0.041 and p-value = 0.011), BKV with larger tumor size (p-value = 0.030), and EBV with family cancer history (p-value = 0.020). In benign tumors, polyomavirus was absent in Hashimoto thyroiditis (p-value = 0.020), BKV was linked to older age (p-value = 0.030), and absence of BKV was associated with COVID-19 vaccination (p-value = 0.046). CONCLUSION: The current study is the first of its kind in Egypt to investigate the prevalence of HPV, EBV, and polyomaviruses in thyroid tumors and to examine their associations with certain clinicopathological characteristics. The findings underline the importance of viral profiling in understanding thyroid tumor behavior and influencing cancer risk as well.
ARNT2-driven transcriptional activation of STRA6 reprograms fatty acid metabolism to promote retroperitoneal liposarcoma progression.
Zhang J, Guo H, Ban B … +8 more , Yang L, Lian J, Li G, Cai L, Deng K, Jiang H, Li X, Wang S
J Cancer Res Clin Oncol · 2025 Oct · PMID 41108418 · Full text
BACKGROUND: Retroperitoneal liposarcoma (RLPS) is a mesenchymal-derived malignant tumor characterized by high aggressiveness and a propensity for local recurrence. Emerging evidence implicates aberrant fatty acid metabol...
BACKGROUND: Retroperitoneal liposarcoma (RLPS) is a mesenchymal-derived malignant tumor characterized by high aggressiveness and a propensity for local recurrence. Emerging evidence implicates aberrant fatty acid metabolism as a key driver of RLPS progression, yet the transcriptional regulators orchestrating this process remain poorly defined. METHODS: Bioinformatics integrating cellular experiments demonstrated the role of fatty acid metabolism in the progression of RLPS. Immunohistochemistry (IHC) and Western blotting (WB) were employed to validate the expression levels of ARNT2, and the role of ARNT2 in tumor progression was demonstrated through CCK8 assays, Transwell invasion assays and wound healing assays. Further experiments confirmed the transcriptional regulatory effect of ARNT2 on STRA6 and demonstrated its control over RLPS progression by modulating intracellular lipid droplet and triglyceride levels. RESULTS: Here, we identify ARNT2 as a novel oncogenic transcription factor that promotes RLPS growth by transcriptionally upregulating STRA6, thereby reprogramming fatty acid metabolism. Specifically, ARNT2 binds to the STRA6 promoter to enhance its activity, thereby upregulating fatty acid metabolic enzymes and promoting lipid droplet accumulation with elevated triglycerides. This metabolic shift fuels energy production and biomass synthesis in RLPS cells, ultimately accelerating tumor proliferation and invasion. CONCLUSION: This study identifies ARNT2 as a transcriptional modulator of fatty acid metabolism pathways, highlighting its potential as a viable molecular target for RLPS therapy.
Running session-conditioned human serum lowers prostate cancer cell spheroid formation.
Baldelli G, Avancini A, Giannarelli D … +11 more , Budel L, Gentilini V, Borsati A, Toniolo L, Conti A, Milella M, Schena F, Brandi G, Pilotto S, De Santi M, Tarperi C
J Cancer Res Clin Oncol · 2025 Oct · PMID 41108364 · Full text
PURPOSE: Physical activity is associated with a lower mortality and recurrence risk in cancer, yet the underlying mechanisms remain unclear. This study aimed to evaluate the effects of running sessions on the tumorigenic...
PURPOSE: Physical activity is associated with a lower mortality and recurrence risk in cancer, yet the underlying mechanisms remain unclear. This study aimed to evaluate the effects of running sessions on the tumorigenic potential of prostate cancer cells using a 3D in vitro model. METHODS: Fifteen healthy males completed two outdoor running sessions (5 km and 10 km), interspersed by 1 month of wash-out time. Blood samples were collected before (PRE), immediately after (POST), and 3 h after (POST-3 h) sessions. Human serum (HS) samples were used to stimulate LNCaP and PC3 cell lines in 3D in vitro culture technique. The spheroid formation ability was quantified after 21 days of incubation, using GelCount. RESULTS: In both prostate cancer cell lines, a reduction in spheroid number was shown, by both running sessions and in all timepoints considered (LNCaP cells: 5 km: - 23.8%; 10 km: - 5.6% POST HS; 5 km: - 37.8%; 10 km: - 34.8% POST-3 h HS; PC3 cells: 5 km: - 14%; 10 km: - 15.9% POST HS; 5 km: - 14.2%; 10 km: - 13% POST-3 h HS). The spheroid volume was reduced by 42.6% (5 km) and 51.1% (10 km) with POST-3 h HS, in LNCaP cells; no significant reduction was observed in PC3 cells. No differences were found between the running sessions, while higher muscle mass, cardiorespiratory fitness and age were associated with greater reductions in spheroid number and volume, especially in LNCaP cells. CONCLUSION: Running sessions reduce prostate cancer cell spheroid formation, especially in participants with higher physical fitness. Shorter running distances showed comparable effects to longer ones, highlighting practical implications for real-world exercise prescriptions in oncology.
A cross-sectional analysis of the global burden of childhood leukemia from 1990 to 2021.
Wang P, Cui J, Ni Z … +6 more , Qian Z, Zhan H, Zhang H, Ye W, Meng W, Bai R
J Cancer Res Clin Oncol · 2025 Oct · PMID 41102585 · Full text
BACKGROUND: Childhood leukemia is a common malignant tumor worldwide, affecting survival rates and posing medical and public health challenges. Assessing its global burden is essential for informing prevention, treatment...
BACKGROUND: Childhood leukemia is a common malignant tumor worldwide, affecting survival rates and posing medical and public health challenges. Assessing its global burden is essential for informing prevention, treatment, and policy efforts. METHODS: This is a cross-sectional study based on data from the 2021 Global Burden of Disease (GBD) study, covering the years 1990 to 2021 and including 204 countries and regions. We analyzed the incidence, mortality, disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) for childhood leukemia. Subgroup analyses were conducted by age, gender, region, and Socio-Demographic Index (SDI) levels to explore disparities and trends. RESULTS: Since 1990, the global burden of childhood leukemia has decreased significantly, with a 59.03% reduction in DALYs. Chronic myeloid leukemia (CML) experienced the largest decline, with incidence, mortality, and DALYs reduced by more than 70%. However, disparities persist: boys generally have a higher burden, and acute lymphoblastic leukemia (ALL) remains the most common subtype. East Asia and Andean Latin America reported the highest burden of ALL in 2021. Incidence is highest in high-SDI regions, but mortality rates decrease as SDI increases. Similar trends were observed for DALYs, with better outcomes in high-SDI regions. CONCLUSIONS: Since 1990, childhood leukemia DALYs decreased by 59.03%, with CML showing the largest decline (> 70% in incidence, mortality, and DALYs). ALL remains the most common subtype, with the highest burden in East Asia and Andean Latin America. High-SDI regions report higher incidence but lower mortality, indicating better outcomes than low-SDI regions.
CAA-derived IL-6 promoted the PD-L1 expression of breast cancer via STAT3/miR-497a-5p signaling.
Zhao C, Zhou X, Li X … +3 more , Li G, Zhang Q, Zhang J
J Cancer Res Clin Oncol · 2025 Oct · PMID 41102510 · Full text
BACKGROUND: Adipocytes are engaged in the development and progression of breast cancer (BC). Cancer-associated adipocytes (CAAs) are specific adipocytes located at the invasive front of BC that modulate tumor behaviors....
BACKGROUND: Adipocytes are engaged in the development and progression of breast cancer (BC). Cancer-associated adipocytes (CAAs) are specific adipocytes located at the invasive front of BC that modulate tumor behaviors. This study aimed to investigate the effect of CAA-derived IL-6 in regulating BC progression. METHODS: Human BC specimens and adipocytes co-cultured with BC cells were used to explore the characteristics of CAAs. Adipocytes and 4T1 cells co-implanted in mouse model and tail vein metastasis model were used to explore the effect of CAAs on malignant progression and immunosuppressive tumor microenvironment (TME) of BC in vivo. The functional assays, flow cytometry, ELISA, miRNAs sequencing and dual-luciferase reporter assay were implemented to investigate the role of CAA-derived IL-6 in regulating programmed cell death protein ligand 1 (PD-L1) expression. RESULTS: CAAs were present at the invasive front of BC with a de-differentiated fibroblast phenotype. CAAs enhanced the malignant behaviors of 4T1 BC cells in vitro, and promoted 4T1 tumor growth and lung metastasis with decreased CD8T cells and upregulated Tregs. The IHC results of both human BC specimens and xenografts showed that CAAs could upregulate PD-L1 expression in BC. Besides, CAAs could secrete abundant IL-6 and thus enhanced PD-L1 expression in 4T1 cells and tumors. More importantly, CAA-derived IL-6 could activate STAT3, while STAT3 blockade in CAA-cultured 4T1 cells upregulated miRNA-497a-5p expression and downregulated PD-L1 expression. Dual-luciferase reporter assay indicated that PD-L1 was a direct target of miRNA-497a-5p. CONCLUSIONS: Our study demonstrated that CAAs promoted the malignant behaviors of BC and enhanced immunosuppression in TME. Specifically, CAA-derived IL-6 promoted the PD-L1 expression of BC via STAT3/miR-497a-5p signaling, thereby contributing to BC progression.
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