Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Cancer Immunol Immunother. 2026 Mar 31;75(4):126. doi: 10.1007/s00262-026-04368-1.

ABSTRACT

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

PMID:41915222 | PMC:PMC13038699 | DOI:10.1007/s00262-026-04368-1

Cancer Immunol Immunother. 2026 Mar 31;75(4):126. doi: 10.1007/s00262-026-04368-1.

ABSTRACT

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

PMID:41915222 | DOI:10.1007/s00262-026-04368-1

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

JHEP Rep. 2026 Mar 23:101824. doi: 10.1016/j.jhepr.2026.101824. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Radiofrequency ablation (RFA) is a widely used treatment for HCC, but its efficacy is often limited by tumor relapse. Neutrophils, serve as a double-edged sword in tumor immunology, have recently been implicated in anti-tumor immunity post-RFA. Shear wave elastography (SWE) is a non-invasive examination for liver tissue, and associated with immune response. This study investigates the correlation between dynamic change of SWE values and neutrophils response following RFA, and explores potential adjuvant strategies for RFA.

METHODS: We conducted a comprehensive analysis using both clinical data from patients undergoing RFA (n=102) and experimental studies in mouse models (n=4-6 per group). Single-cell RNA sequencing (scRNA-seq) and multi-omics analyses including multiplex immunofluorescence staining and flow cytometric analysis were performed to identify neutrophil subsets. To assess the therapeutic potential of neutrophils-activating therapy for enhancing anti-tumor immunity post-RFA, we tested CD40 agonist in combination with RFA in preclinical models.

RESULTS: We noticed that rising liver SWE values following RFA were significantly associated with reduce relapse (n=102, p<0.001), and demonstrated that this phenomenon was linked to the inflammatory environment induced by the infiltration of neutrophils (2.5-fold increase, p<0.001). scRNA-seq analysis identified neutrophil subsets characterized by high expression of interferon-stimulated genes, which exhibited potent anti-tumor activity via nitric oxide. Importantly, treatment with CD40 agonist significantly augmented this immune response, leading to reduced tumor growth in mice (149.6±38.12 mm³ vs 23.92±4.43 mm³, p=0.008).

CONCLUSIONS: We linked clinical features to neutrophil-mediated immunity post-RFA. Neutrophil-activating therapy like CD40 agonists may prevent HCC relapse after RFA.

PMID:41881314 | DOI:10.1016/j.jhepr.2026.101824