Immunology[JOURNAL]
Sun
200 papers
Comment on: Pasco ST Et Al. "Challenge-Specific Modulation of Responses to Adjuvant-Induced Innate Immune Memory".
Vijayasimha M, Srikanth M
Immunology · 2026 Apr · PMID 41630565 · Publisher ↗
This schematic illustrates the role of endoplasmic reticulum (ER) stress and PERK inhibition in modulating pancreatic cancer cell fate. ER stress activates the PERK pathway, which contributes to tumor cell survival. Phar...
This schematic illustrates the role of endoplasmic reticulum (ER) stress and PERK inhibition in modulating pancreatic cancer cell fate. ER stress activates the PERK pathway, which contributes to tumor cell survival. Pharmacologic inhibition of PERK, as depicted, leads to two downstream effects: decreased cellular proliferation and increased apoptosis. The diagram highlights the therapeutic potential of PERK-targeting strategies in disrupting cancer cell growth and promoting programmed cell death.
Comparative efficacy and safety of IL-17 and IL-23 inhibitors for moderate-to-severe psoriasis in Asian populations: a systematic review and meta-analysis.
Alzghool M, Jiquan S, Bashir MB
BMC Immunol · 2026 Feb · PMID 41629781 · Full text
BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting a significant portion of the global population. Biologics targeting the IL-17 and IL-23 pathways are effective in treating moderate-to-severe psoria...
BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting a significant portion of the global population. Biologics targeting the IL-17 and IL-23 pathways are effective in treating moderate-to-severe psoriasis; however, most clinical trials have been conducted in Western populations, leaving limited data on their efficacy and safety in Asian populations. Ethnic differences due to genetic and environmental factors can influence treatment responses. This meta-analysis evaluates the efficacy and safety of IL-17/23 inhibitors in Asian patients with moderate-to-severe psoriasis. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2019 and 2025 was conducted in accordance with the PRISMA 2020 guidelines. Comprehensive searches were performed in PubMed, Embase, Scopus and clinicaltrial.gov databases to identify studies evaluating IL-17 and IL-23 inhibitors in Asian adults with moderate-to-severe psoriasis. Eligible studies compared these biologics with placebo or active comparators. The primary outcome was treatment efficacy, assessed by improvement in Psoriasis Area and Severity Index (PASI). Secondary outcomes included treatment-emergent adverse events (AEs). Data were pooled using random-effects models, and results were expressed as Odds ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 30 randomized controlled trials (RCTs) involving 14,000 Asian and mixed-ethnicity participants were included. The meta-analysis demonstrated a significant overall efficacy advantage of IL-17 and IL-23 inhibitors over placebo or active comparators (log OR = 1.25; 95% CI 0.98–1.52; p < 0.0001). Subgroup analyses confirmed consistent treatment responses across efficacy measures—PASI 75 (log OR = 1.36; 95% CI 0.97–1.75; I² = 64.5%) and PASI 90 (log OR = 1.23; 95% CI 0.87–1.58; I² = 92.4%)—as well as across biologic classes (IL-17: log OR = 1.43 [1.09–1.77]; IL-23: log OR = 1.04 [0.60–1.49]). When stratified by population, efficacy remained high among Asian cohorts (log OR = 1.40 [1.17–1.62]) and mixed populations (log OR = 1.08 [0.51–1.65]). Safety analyses showed that treatment-emergent adverse events (TEAEs) were mostly mild to moderate (50–85% for IL-17, 64–92% for IL-23), and serious adverse events (SAEs) occurred in < 5% of patients, without treatment-related deaths or unexpected immune-mediated events. CONCLUSIONS: IL-17 and IL-23 inhibitors demonstrate high efficacy and favorable safety profiles in Asian adults with moderate-to-severe psoriasis, consistent with global evidence. Both biologic classes achieved substantial clinical improvements in PASI with low rates of serious adverse events.
Saussurea involucrata oral liquid alleviates joint inflammation in CIA rats by modulating macrophage polarization and glucose metabolism.
Maimaitituersun S, Mijiti W, Cong S … +4 more , Zhao X, Zhou Z, Ji P, Luo L
BMC Immunol · 2026 Feb · PMID 41629777 · Full text
OBJECTIVE: To evaluate the therapeutic effects of Saussurea involucrata Oral Liquid (SIOL) in a collagen-induced arthritis (CIA) rat model. METHODS: This study was conducted from April 2023 to June 2024. Sixty male SPF S...
OBJECTIVE: To evaluate the therapeutic effects of Saussurea involucrata Oral Liquid (SIOL) in a collagen-induced arthritis (CIA) rat model. METHODS: This study was conducted from April 2023 to June 2024. Sixty male SPF SD rats were randomly divided into six groups: control, model, tripterygium glycosides tablet (TGT) group, and low, medium, and high doses of SIOL. CIA was induced by subcutaneous injection of bovine type II collagen (CII) and incomplete Freund’s adjuvant (IFA). Treatment groups received corresponding doses of SIOL or TGT. Therapeutic efficacy was assessed through body weight, arthritis index (AI), ankle diameter, and toe volume. Joint tissue pathology, serum and synovial inflammatory factors, macrophage polarization, and plasma metabolites were analyzed using H&E staining, ELISA, flow cytometry, Western blotting, and LC–MS. RESULTS: SIOL significantly reduced AI, ankle diameter, toe volume, and pathological scores compared to the model group. SIOL also decreased serum and synovial proinflammatory factors TNF-α, IL-6, and IL-1β while increasing anti-inflammatory IL-10 and IL-4. Medium and high doses of SIOL notably lowered M1 macrophage markers CD86 and iNOS, while elevating M2 markers CD163 and Arg-1. No significant differences were observed between the medium/high SIOL and TGT groups regarding therapeutic effects. Additionally, SIOL (high dose) markedly reduced glucose metabolism-related plasma metabolites, particularly key metabolites in the TCA cycle. A significant correlation was found between macrophage polarization, inflammatory markers, and metabolite levels. CONCLUSION: SIOL alleviates joint inflammation in CIA rats, which is associated with modulation of macrophage polarization and alterations in glucose metabolism.
BXSB.Yaa: A Translational Model of Toll-Like Receptor 7-Type I Interferon-Driven Systemic Lupus Erythematosus.
Sison B, Farley CM, Wilson JJ … +3 more , Lakshminarayanan S, Roopenian DC, Chang CH
Immunology · 2026 Feb · PMID 41629129 · Publisher ↗
Despite recent approvals of belimumab and anifrolumab, durable, steroid-sparing remission in systemic lupus erythematosus (SLE) remains uncommon, underscoring ongoing therapeutic needs. The BXSB.Yaa mouse model, harbouri...
Despite recent approvals of belimumab and anifrolumab, durable, steroid-sparing remission in systemic lupus erythematosus (SLE) remains uncommon, underscoring ongoing therapeutic needs. The BXSB.Yaa mouse model, harbouring Y-linked Tlr7 duplication on a polygenic susceptibility background, has been instrumental in elucidating the TLR7-type I interferon (IFN1) axis central to SLE. This review positions BXSB.Yaa as a comparative model system and advances a mechanism-aligned framework that maps murine models to human SLE endotypes (e.g., IFN1-high vs. IFN-γ-dominant; germinal center- vs. extrafollicular-biased B-cell responses) and links those endotypes to targeted interventions. We highlight the fidelity of BXSB.Yaa to IFN1-high patient biology, and its contributions of polygenic susceptibility in driving immune cell dysregulation, cytokine imbalance, and therapeutic responsiveness to BAFF and IFN1 blockade. Notably, this model also recapitulates pathogenic pDC activation, highlighting its relevance for emerging pDC-targeted strategies. By contrasting BXSB.Yaa with other prominent lupus-prone strains (e.g., MRL/lpr, NZBWF1, NZM2410, B6.SLE1/2/3, BXD2, and Kika), we benchmark its predictive value for clinical heterogeneity and treatment response. We synthesise insights from BXSB.Yaa studies, including those that informed FDA-approved biologics, and discuss implications for next-generation precision therapies. Collectively, we advocate for BXSB.Yaa as an essential pre-clinical platform among complementary models to accelerate mechanism-based drug development and enable stratified translation in SLE research.
Polypore mushroom mycelia as an adjunct to COVID-19 vaccination: a randomized clinical trial.
Saxe G, Smith CN, Golshan S … +10 more , Shekhtman T, Bair ZJ, Beathard C, Davis RA, MacElhern L, Shubov A, Slater D, Kao LK, Senowitz P, Wilson S
BMC Immunol · 2026 Jan · PMID 41620671 · Full text
BACKGROUND: Use of fungal mycelium as a vaccination adjunct may constitute a novel antiviral strategy to address newly emerging viruses. We evaluated safety and feasibility of a fungal mycelium-based natural product (Fom...
BACKGROUND: Use of fungal mycelium as a vaccination adjunct may constitute a novel antiviral strategy to address newly emerging viruses. We evaluated safety and feasibility of a fungal mycelium-based natural product (Fomitopsis officinalis and Trametes versicolor, FoTv) as an adjunct to human COVID-19 vaccination, as well as its impact on vaccine side-effects and anti-SARS-CoV-2 antibodies (Abs). METHODS: Randomized, double-blind, placebo-controlled clinical trial involving adjunctive treatment with FoTv or visually-identical Placebo (dosage: eight 500-mg capsules TID orally for four days) in combination with COVID-19 vaccination. Main outcomes included: Safety (adverse events, renal and hepatic function [Days 1–14]); Feasibility (completion rate and treatment adherence); Side-effects (number and severity, self-reported on days 1 [vaccination] to 5); and anti-SARS-CoV-2 Ab levels (receptor-binding domain and Spike, collected from blood drawn on days 1, 3, 14, and 28/42, and at 6 months). RESULTS: Ninety participants receiving COVID-19 vaccination were randomized to either FoTv (N = 52) or Placebo (N = 38) groups. There were no adverse events and the groups had overlapping 95% confidence intervals for the percentage of participants transitioning from normal to abnormal renal/hepatic function when comparing Days 1 and 14. All participants (100%) completed the study and treatment adherence was greater than 95%. Participants with detectable anti-SARS-CoV-2 Abs (from prior COVID antigen exposure) were classified as “COVID-Exposed” and those with undetectable anti-SARS-CoV-2 Abs as “COVID-Naive.” FoTv, versus Placebo, significantly reduced side-effects in COVID-Naive individuals, specifically on days 3 and 5, but not in COVID-Exposed individuals. In the COVID-Naive FoTv group, Ab responses were preserved across 6 months (and possibly increased), an effect not observed among other groups. CONCLUSIONS: After COVID-19 vaccination, adjunctive FoTv was safe, feasible, and reduced vaccine side-effects without compromising (and possibly increasing) Ab levels up to 6 months in participants without previous SARS-CoV-2 exposure. Use of fungal mycelia was successfully tested as a unique approach to prevent a novel pandemic virus (SARS-CoV-2), with potential application to H5N1/Bird Flu and other emerging viruses. TRIAL REGISTRATION: Trial registered on ClinicalTrials.gov NCT04951336 on June 30, 2021.
Association between gut microbiota-derived TMAO, systemic inflammatory markers, and echocardiographic findings in patients with common variable immunodeficiency.
Uğraklı S, Çölkesen F, Tatar S … +5 more , Gerek ME, Arslan Ş, Göktaş E, Topcu C, Feyzioğlu B
BMC Immunol · 2026 Jan · PMID 41620646 · Full text
BACKGROUND: Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. While infections are common, over 50% of patients exhibit autoimmune and immune activation related co...
BACKGROUND: Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. While infections are common, over 50% of patients exhibit autoimmune and immune activation related complications. Chronic inflammation from dysbiosis may affect the heart in CVID, though its relationship with gut barrier and echocardiographic findings is still unclear. This study investigates the associations between intestinal permeability, Trimethylamine N-oxide (TMAO) levels, immune activation, and cardiac function in CVID patients. METHODS: The study included 31 CVID patients and 31 matched healthy controls. Serum zonulin, TMAO, soluble CD14 (sCD14), soluble CD25 (sCD25), Tumor Necrosis Factor-alpha (TNF-α), and IL-17 A levels were measured by ELISA. Cardiac function was assessed using speckle-tracking echocardiography (STE), focusing on global longitudinal strain (GLS). RESULTS: Increased levels of zonulin and TMAO were observed in CVID patients. sCD14 and sCD25 levels correlated strongly with TMAO. TMAO showed a negative correlation with Ejection Fraction and a positive correlation with Pulmonary Artery Pressure (PAP). No significant differences were found in serum TNF-α and IL-17 A levels in the compared groups. Compared to the control group (-19.90 ± 2.41), a remarkable reduction in mean GLS (-18.13 ± 3.13) was determined in the CVID group. These results are early indicators of myocardial dysfunction. Strain analysis showed a significant decrease in negative Apical 4-Chamber View Basal Longitudinal Strain (AP4B) and Apical 3-Chamber View Basal Longitudinal Strain AP3B values in the CVID group (p = 0.012 and p = 0.027). CONCLUSIONS: In this study, elevated serum zonulin and TMAO levels correlated with increased intestinal permeability and immune activation in CVID. High TMAO was linked to early myocardial dysfunction, highlighting the potential of microbiome-targeted therapies and advanced echocardiography for early cardiac risk detection in CVID.
Genetic Determinants of Peanut-Specific IgG4 Levels in the Context of Sustained Oral Peanut Exposure in the LEAP Study.
Kanchan K, Cerosaletti K, Perry JA … +12 more , DuToit G, Manohar M, Ling H, Paschall JE, Sanda S, Chinthrajah RS, Nepom GT, Nadeau KC, Jones SM, Lack G, Ruczinski I, Mathias RA
Immunology · 2026 Jun · PMID 41615410 · Full text
In the Learning Early About Peanut Allergy (LEAP) study, participants in the peanut consumption group, at 60 months of age, had higher levels of peanut-specific IgG4 (psIgG4), a biomarker of immune modulation, compared t...
In the Learning Early About Peanut Allergy (LEAP) study, participants in the peanut consumption group, at 60 months of age, had higher levels of peanut-specific IgG4 (psIgG4), a biomarker of immune modulation, compared to those in the peanut-avoidance group. We investigated the genetic determinants of psIgG4 among participants who consumed peanuts. Using whole-genome sequencing data, we performed a genome-wide association study (GWAS) for psIgG4 in the LEAP peanut consumption group participants (N = 267). We generated a cumulative genetic score from the identified loci and evaluated its association with psIgG4 levels in LEAP. The association was then assessed for replication in two independent peanut oral immunotherapy (PnOIT) trials, IMPACT and POISED. We identified 45 variants that reached suggestive significance (p < 1 × 10), mapping to 17 independent loci in the LEAP peanut consumption group; none of these variants were associated with the psIgG4 levels in the avoidance group, highlighting a potential gene-by-environment (GxE) interaction. One locus on chromosome 2 showed regulatory signatures for SEPT2, a gene involved in epithelial barrier function. The genetic score was significantly associated with psIgG4 among LEAP consumers (β = 0.433; p = 1.20 × 10) in the discovery cohort and IMPACT PnOIT participants (β = 0.287; p = 0.02) in an independent testing cohort. No association was observed in older POISED PnOIT participants (β = -0.029; p = 0.79). Identification of the SEPT2 locus in participants protected from peanut allergy (PA) suggests involvement of epithelial barrier pathways in modulating immune responses. Findings across all three trials emphasise the importance of GxE interactions, specifically the interplay between genetics and oral peanut exposure. Taken together, the findings indicate that early, sustained peanut consumption, combined with genetic factors, promotes a protective immune response to peanut allergens. Trial Registration: LEAP: NCT00329784; IMPACT: NCT03345160; POISED, NCT02103270.
The correlation between the systemic immune-inflammation index and relapse and metastasis in cervical squamous cell carcinoma patients over 50 years and older.
Jiao Y, He Y, Zhao B … +1 more , Sha L
BMC Immunol · 2026 Jan · PMID 41612188 · Full text
OBJECTIVE: The aim of this study was to confirm the association of systemic immune-inflammation index (SII) with relapse and metastasis of cervical squamous cell carcinoma (CSCC) in patients over 50 years and older. METH...
OBJECTIVE: The aim of this study was to confirm the association of systemic immune-inflammation index (SII) with relapse and metastasis of cervical squamous cell carcinoma (CSCC) in patients over 50 years and older. METHODS: This retrospective study included 470 patients aged 50 years and older with CSCC who were treated at the Second Affiliated Hospital of Dalian Medical University between January 2020 and January 2023. The patients were divided into two groups according to median SII: high SII (n = 235) and low SII (n = 235). Univariate and multivariate logistic regression analysis, subgroup analysis, and receiver operating characteristic curve (ROC) analysis were used to explore the association of SII with relapse and metastasis. RESULTS: The total population was 470, of which 161 (34%) relapsed and 133 metastasized (28.3%). Compared with low SII, high SII group had higher probability of relapse and metastasis (P < 0.05). Multivariate logistic regression analysis showed that, after adjusting for all confounding factors, each additional standard deviation in SII increased the risk of relapse by 28.5%, and the risk of relapse was 1.568 times higher for high SII than for low SII (P < 0.05). In addition, each additional unit in logSII and LnSII increased the risk of metastasis by 178.4% and 56%, respectively (P < 0.05). Moreover, in subgroups of patients aged 65 years or older, postmenopausal, with uterine fibroids, without HPV infection, without hypertension, without diabetes, and without undergoing radical cervical cancer, higher levels of SII remained significantly associated with an increased risk of metastasis (P < 0.05). In addition, ROC analysis indicated that SII had a certain predictive value for both relapse and metastasis (AUC = 0.599 and 0.617). CONCLUSION: Higher levels of SII are significantly associated with a higher risk of relapse and metastasis, indicating that SII may have important clinical value in the prognosis assessment of CSCC.
Mitochondrial DNA: A Key Alarmin Igniting the Inflammasome Fire in Health and Disease.
Park WH
Immunology · 2026 Jun · PMID 41611232 · Publisher ↗
Beyond their classical role as cellular powerhouses, mitochondria are now recognised as indispensable hubs for innate immune signalling. A pivotal aspect of this function is the release of mitochondrial DNA (mtDNA), a po...
Beyond their classical role as cellular powerhouses, mitochondria are now recognised as indispensable hubs for innate immune signalling. A pivotal aspect of this function is the release of mitochondrial DNA (mtDNA), a potent damage-associated molecular pattern (DAMP) that, when misplaced, acts as a powerful alarmin due to its prokaryotic origins. In response to cellular stress or infection, mtDNA translocates to the cytosol and activates intracellular protein platforms known as inflammasomes, triggering the maturation of cytokines like interleukin-1β (IL-1β) and inducing a lytic form of cell death, pyroptosis. This review synthesises current research on this intricate relationship. Whilst potassium (K) efflux remains the canonical trigger for the NLR family pyrin domain containing 3 (NLRP3) inflammasome, emerging and debated roles of oxidised mtDNA (ox-mtDNA) as a potential direct ligand or critical upstream amplifier are explored. The manuscript elucidates mtDNA release mechanisms, such as mitochondrial permeability transition pore (mPTP) opening, and explores the role of amplifying pathways like the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis and cytidine/uridine monophosphate kinase 2 (CMPK2)-mediated mtDNA synthesis. The profound involvement of the mtDNA-inflammasome axis is surveyed across a spectrum of pathologies, including autoimmune, metabolic, neurodegenerative, and cardiovascular diseases. The compiled evidence establishes mtDNA as a universal trigger of inflammation and a unifying pathogenic driver across this diverse disease landscape, highlighting the significant therapeutic potential of modulating this fundamental immune signalling axis to treat a multitude of human diseases.
Exploring the Gut Ecosystem: Mechanism Studies From the Gut Microbiota to Inflammatory Cytokines to Inflammatory Bowel Disease.
Tang B, Cheng W, Gu A … +3 more , Miao Y, Yu G, Chen J
Immunology · 2026 Jun · PMID 41609125 · Publisher ↗
A potential association exists among gut microbiota, inflammatory mediators and inflammatory bowel disease (IBD), yet the precise biological mechanisms underlying these interconnections remain to be fully elucidated. Sin...
A potential association exists among gut microbiota, inflammatory mediators and inflammatory bowel disease (IBD), yet the precise biological mechanisms underlying these interconnections remain to be fully elucidated. Single nucleotide polymorphisms (SNPs) associated with gut microbiota were collected from the MiBioGen consortium. SNPs associated with IBD were sourced from GWAS research. Furthermore, a two-step MR approach was employed to clarify the potential mediating role of inflammatory factors in the causal relationship between gut microbiota and IBD. The genus Eubacterium ruminantium group (odds ratio [OR] = 1.087, 95% confidence interval [CI], 1.006-1.174, p = 0.035), genus Lachnospiraceae FCS020 group (OR, 1.172, 95% CI, 1.035-1.326, p = 0.012) were identified as a risk factor for IBD. Conversely, the family Bifidobacteriaceae performed a suggestively positive impact on the protective role against IBD (OR, 0.834, 95% CI, 0.728-0.956; p = 0.009), as well as family Clostridiaceae1 (OR, 0.827, 95% CI, 0.710-0.965; p = 0.016), family Lactobacillaceae (OR, 0.889, 95% CI, 0.798-0.991; p = 0.033) were found to be protective factors. Furthermore, our study indicated that the genus Lachnospiraceae FCS020 group contributed to the risk of IBD by affecting Interleukin-18 (IL-18), a mediation effect (OR = 1.015, 95% CI, 1.000-1.037, mediation proportion = 9.494%). This study offers genetic evidence from the perspective of bioinformatics to support potential causal mechanisms linking gut microbiota and IBD. Furthermore, from the perspective of gene prediction, it revealed the mediating role of IL-18 in the pathogenicity of the gut microbiota on IBD.
Type I interferonopathy in ATR-X syndrome reveals a transcriptional role for cGAS.
Geltman R, Bogunovic D
Nat Rev Immunol · 2026 Mar · PMID 41606192 · Publisher ↗
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Phylogeny-guided multi-epitope vaccine design targeting conserved and divergent regions of Brucella OMP2, OMP25, and OMP31: an immunoinformatics study.
Doostmohammadi A, Samimi Hashjin A, Shahbazi B … +4 more , Ahmadi K, Rostamian M, Majidian M, Madanchi H
BMC Immunol · 2026 Jan · PMID 41593501 · Full text
Brucella is a zoonotic intracellular bacterial pathogen. Currently, no human vaccines for brucellosis are approved, and only animal vaccines are available. Despite the widespread use of live attenuated vaccines, several...
Brucella is a zoonotic intracellular bacterial pathogen. Currently, no human vaccines for brucellosis are approved, and only animal vaccines are available. Despite the widespread use of live attenuated vaccines, several drawbacks have prompted investigation into outer membrane proteins (OMPs) as potential vaccine candidates. This study employs immunoinformatics to design a multi-epitope vaccine targeting conserved regions of the OMP2a, OMP2b, OMP1, OMP25, and OMP31 antigens against four common Brucella species. Helper T-lymphocyte (HTL), Cytotoxic T-lymphocyte (CTL), and B-cell epitopes of OMP31, OMP25, OMP2a, and OMP10 were predicted and analyzed. The selected epitopes form a multi-epitope design featuring a flexible linker, “GGSSGG,” which connects the epitopes. This construct was fused to the Cholera Toxin B subunit (CtxB) at the N-terminus as an adjuvant, while a His-tag at the C-terminus facilitates purification. The tertiary structure of the multi-epitope was then modeled and refined. The 3D structure and its sequence were evaluated for physicochemical properties, structural features, in silico cloning, B epitope prediction, immune response simulation, and molecular docking with toll-like receptors (TLRs). The stability of the construct-TLR interactions was assessed through molecular dynamics (MD) simulations. The final vaccine construct demonstrated antigenicity and non-allergenicity, along with satisfactory physicochemical properties, as it binds to TLR2/4 receptors and induces an in-silico immune response. MD simulations confirmed the stability of the docked complexes. While this multi-epitope vaccine candidate shows promise in eliciting various immune responses against brucellosis in silico, it is crucial to validate its efficacy through laboratory and animal model testing.
The efficacy analysis of immunotherapy rechallenge after progression from first-line chemo-immunotherapy in advanced non-small cell lung cancer.
Shi W, Kong R, Xiong J … +3 more , Peng Y, Yang Z, Huang Y
BMC Immunol · 2026 Jan · PMID 41593475 · Full text
INTRODUCTION: Combining immune checkpoint inhibitors (ICI) with chemotherapy has been established as the standard first-line (1 L) treatment for advanced non-small cell lung cancer (NSCLC). However, the optimal second-li...
INTRODUCTION: Combining immune checkpoint inhibitors (ICI) with chemotherapy has been established as the standard first-line (1 L) treatment for advanced non-small cell lung cancer (NSCLC). However, the optimal second-line (2 L) treatment following 1 L chemo-immunotherapy remained controversial. METHODS: Patients with advanced NSCLC who progressed following 1 L chemo-immunotherapy and continued to receive ICI as 2 L therapy were enrolled in the study. These patients were divided into two groups according to the therapeutic modality: chemo-immunotherapy plus anti-angiogenesis therapy group (CIA group) and chemo-immunotherapy group (CI group). Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) to minimize selection bias before comparative analyses. The efficacy of immunotherapy rechallenge combination therapy was evaluated based on overall survival (OS) and progression-free survival (PFS). Cox proportional hazards regression analyses were applied to determine predictive factors independently associated with survival outcomes. RESULTS: A total of 101 patients were enrolled in this study, 45 patients were enrolled in CIA group, and those who didn’t receive anti-angiogenesis drugs were defined as CI group (n = 56). Overall, Immunotherapy rechallenge reached a median OS of 19.47 months and median PFS of 7.10 months. The CIA group showed significantly longer PFS than the CI group (11.49 vs. 6.06 months, p = 0.03). Similar results in PFS were observed in the study cohorts balanced with IPTW (11.49 vs. 6.89, p = 0.01). Multivariate analyses revealed that prior immunotherapy response and smoking status could be independent prognostic factors for PFS. CONCLUSIONS: Immunotherapy rechallenge could bring survival benefits following progression under chemo-immunotherapy, especially those who responded to prior immunotherapy. Additionally, the use of anti-angiogenesis drugs could significantly improve the clinical response of immunotherapy rechallenge.
Germinal centre IL-4 enforces tissue confinement of IgE memory.
Baronijan L, Martin A
Nat Rev Immunol · 2026 Mar · PMID 41593223 · Publisher ↗
Abstract loading — click title to view on PubMed.
TREM-1 Blockade Inhibits Inflammasome Activation and Pyroptosis: Novel Insights on the Role of TREM-1 and Syk in Monosodium Urate Crystal-Induced Inflammation.
Molad Y, Lagovsky I, Kliminski V
Immunology · 2026 Jun · PMID 41582609 · Full text
Gout is associated with the upregulation of triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble TREM-1 (sTREM-1). Cell activation signalling induced by monosodium urate (MSU) crystals and TREM-1 signall...
Gout is associated with the upregulation of triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble TREM-1 (sTREM-1). Cell activation signalling induced by monosodium urate (MSU) crystals and TREM-1 signalling both converge on spleen tyrosine kinase (Syk). The aim of this study was to decipher the role of the TREM-1 peptidomimetic inhibitor LP17, as well as Syk inhibitor, and their interaction during MSU-induced cell inflammation, focusing on NLRP3 inflammasome activation, IL-1β production and pyroptosis. In MSU-activated cells, both LP17 and Syk inhibitor (iSyk) significantly reduced the secretion of IL-1β and the release and activity of caspase-1. LP17 changed the phosphorylation of Syk, indicating that inhibition of TREM-1 modulates the activation state of Syk. Both LP17 and iSyk reduced the level of NLRP3-induced apoptosis-associated speck-like protein (ASC) transcripts and MSU-induced immunolabelling of ASC. Under confocal immunomicroscopy, TREM-1 in MSU-crystal-activated cells was localised to the same perimembranal compartment with NLRP3 inflammasome; inhibition of TREM-1 hindered the colocalisation of Syk with ASC. These results were corroborated by use of the in vitro ASC oligomerszation assay that showed that blocking TREM-1 induced Syk redistribution from ASC complexes, indicating that LP17 can repress the ability of Syk to incorporate into the forming ASC speckle. Additionally, unlike iSyk, LP17 hampered MSU-induced cleavage of gasdermin D, the hallmark of pyroptosis. Together, our findings suggest that blocking TREM-1 may prove beneficial as a novel strategy in the treatment of gout as well as other inflammasome-mediated diseases.
Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.
Keat SBK, Khatri P, Ali YM … +12 more , Arachchilage CH, Demopulos G, Baillie K, Miners KL, Ladell K, Jones SA, Davies HE, Price DA, Zelek WM, Morgan BP, Schwaeble WJ, Lynch NJ
Immunology · 2026 Jun · PMID 41581925 · Full text
Long COVID affects a substantial proportion of survivors of acute infection with severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), who suffer a variety of symptoms that limit their quality of life...
Long COVID affects a substantial proportion of survivors of acute infection with severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), who suffer a variety of symptoms that limit their quality of life and economic activity. Although the aetiology of long COVID is obscure, it appears to be a chronic inflammatory condition. Complement dysregulation is a prevalent feature of long COVID. Specifically, markers of classical, alternative, and terminal pathway activation are often elevated in patients with this condition. Here, we used a sensitive assay for mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes to analyse lectin pathway activation in a previously characterised cohort of patients with long COVID (n = 159) and healthy convalescent individuals with no persistent symptoms after infection with SARS-CoV-2 (n = 76). The data were combined with those from the most predictive complement analytes identified previously to delineate potential biomarkers of long COVID. MASP-2/C1Inh complexes were significantly elevated in patients with long COVID (p = 0.0003). Generalised linear modelling further identified an optimal set of four markers, namely iC3b (alternative pathway), TCC (terminal pathway), MASP-2/C1Inh (lectin pathway), and the complement regulator properdin, which had a receiver operating characteristic predictive power of 0.796 (95% confidence interval = 0.664-0.905). Combinations of the classical pathway markers C4, C1q, and C1s/C1Inh were poorly predictive of long COVID. These findings demonstrate that activation of the lectin complement pathway, which occurs upstream of the alternative and terminal pathways and can be inhibited therapeutically, is a salient feature of long COVID.
PHLDB1 and WDFY4 as dual-state biomarkers in SLE pathogenesis and lupus nephritis prediction.
Zhai J, Zhang L, Jia W … +4 more , Pan Y, Zhang P, Zou Q, Wu Y
BMC Immunol · 2026 Jan · PMID 41578171 · Full text
OBJECTIVES: Our previous study confirmed systemic lupus erythematosus (SLE) associated with polymorphisms of PHLDB1 and WDFY4 genes. In this study, we investigatedthe clinical relevance of PHLDB1 and WDFY4 in SLE pathoge...
OBJECTIVES: Our previous study confirmed systemic lupus erythematosus (SLE) associated with polymorphisms of PHLDB1 and WDFY4 genes. In this study, we investigatedthe clinical relevance of PHLDB1 and WDFY4 in SLE pathogenesis and their potential as biomarkers. METHODS: A total of 634 SLE patients from Sichuan University West China Hospital and 400 age- and sex-matched healthy controls were included in this study. Serum PHLDB1 and WDFY4 of SLE patients and HCs were measured by ELISA, and the laboratory indicators were collected through the electronic medical record. LASSO, logistic regression, and random forest models for SLE diagnosis and LN prediction, including variables: age, sex, serum proteins (PHLDB1/WDFY4), genotypes, cytokines, and clinical markers. RESULTS: Results revealed elevated PHLDB1 in SLE patients compared to controls (1.61 vs. 1.48 ng/mL, P = 0.025), while paradoxically showing suppression in LN versus Non-LN patients (1.42 vs. 1.52 ng/mL, P = 0.031). WDFY4 specifically increased in LN (666.59 vs. 594.57 pg/mL, P < 0.001) without systemic SLE alterations. Machine learning models incorporating these biomarkers demonstrated diagnostic utility, with random forest achieving AUC 0.843 for SLE discrimination and AUC 0.990 for LN prediction. LN patients concurrently exhibited distinct immune dysregulation (reduced IL-6/IL-17 and elevated TNF-α/IL-18) and renal metabolic impairment. These findings position PHLDB1 as a systemic SLE biomarker and WDFY4 as a LN-specific blood indicator, showing promise for clinical subtyping applications. Further validation of these stratified biomarkers is warranted. CONCLUSION: Our results confirm a correlation between the serum levels of PHLDB1 and the occurrence of SLE.
Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy.
Zak J, Teijaro JR
Nat Rev Immunol · 2026 Jun · PMID 41577820 · Full text
JAK inhibitors target a large group of cytokines that signal through the JAK-STAT pathway and are typically used clinically as immunosuppressive agents. However, recent work has demonstrated the paradoxical ability of JA...
JAK inhibitors target a large group of cytokines that signal through the JAK-STAT pathway and are typically used clinically as immunosuppressive agents. However, recent work has demonstrated the paradoxical ability of JAK inhibitors to enhance antitumour and antiviral immune responses and established their synergy with immune checkpoint inhibitors in early-stage clinical trials. In this Perspective, we consider why JAK inhibitors, which are typically used as immunosuppressive drugs, can have immune-enhancing effects, exploring the potential mechanistic basis and the opportunities to harness this effect to improve cancer immunotherapy.
Eosinophil Biology Today-A Primer for Basic and Clinical Investigators.
Vieira BM, Xavier-Elsas P, Moura-Neto V … +1 more , Gaspar-Elsas MIC
Immunology · 2026 May · PMID 41574938 · Publisher ↗
Eosinophils are multifunctional granulocytes that participate in tissue homeostasis, host defence, inflammation, and repair. Their activities are now known to extend beyond type-2 immunity and include the release of dive...
Eosinophils are multifunctional granulocytes that participate in tissue homeostasis, host defence, inflammation, and repair. Their activities are now known to extend beyond type-2 immunity and include the release of diverse cytokines and growth factors, such as IL-4, IL-13, TGF-β, IL-1β, GM-CSF, and TNF-α, together with context-dependent immunomodulatory, cytotoxic, and pro-remodelling functions. Recent advances highlight the importance of tissue imprinting and microenvironmental cues in shaping eosinophil phenotypes, revealing substantial functional plasticity and transcriptional diversity across physiological and pathological settings. Here we synthesise essential concepts in eosinophil biology and provide an overview of the most widely used approaches for visualising, isolating, and functionally characterising these cells, emphasising methodological strengths, limitations, and common artefacts. We further outline how transcriptomic and proteomic tools have refined the understanding of eosinophil phenotypes and their relevance to disease, including allergy, infection, tissue repair, and cancer. Overall, we provide a resource for basic and clinical investigators who are not currently working in eosinophil biology, but might be attracted to this multidisciplinary area in view of many recent exciting developments.
Infused PMN-MDSCs from G-CSF-mobilized PBSCs protect against II-IV° acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Chen M, Wang XQ, Long J … +4 more , Fu MJ, Wang H, Li Y, Zhao W
BMC Immunol · 2026 Jan · PMID 41572151 · Full text
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells. Their role in modulating acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-...
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells. Their role in modulating acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This study aimed to investigate the impact of MDSC levels in granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood stem cell (PBSC) grafts on the incidence of II–IV° aGVHD. RESULTS: We retrospectively analyzed 170 allo-HSCT recipients. Employing an exposure-based analytical framework, patients were stratified into high- and low-dose groups based on the infused dose of polymorphonuclear MDSCs (PMN-MDSCs). In Fine-Gray competing risk analyses, a high dose of PMN-MDSCs per kilogram (> 17.5 × 10⁶/kg) was an independent protective factor against aGVHD (subdistribution hazard ratio [sHR] 0.25, 95% CI 0.07–0.88, P = 0.039). A clinically applicable optimal cut-off was identified at 11.3 × 10⁶/kg. Patients receiving a PMN-MDSC dose > 11.3 × 10⁶/kg had significantly superior 300-day overall survival (92.4% vs. 74.9%, P = 0.005) and GVHD-free relapse-free survival (76.3% vs. 40.4%, P < 0.001) compared to the low-dose group. In the malignant disease subset (n = 147), a high dose of the activated LOX-1⁺ PMN-MDSC subset was associated with a markedly lower cumulative incidence of relapse (1.37% vs. 11.42%, P = 0.015). Longitudinal monitoring revealed that the peak incidence of aGVHD (median day + 29) closely followed the peak and subsequent decline of circulating MDSC levels. CONCLUSIONS: The absolute dose of PMN-MDSCs in G-CSF-mobilized grafts is an independent determinant of II–IV°aGVHD risk and survival outcomes, with a defined threshold of 11.3 × 10⁶/kg. These findings position PMN-MDSC dose as a promising biomarker for risk stratification and a potential lever for optimizing graft composition in allo-HSCT.
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