ArticleJCI insight2018
Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The trial behind it
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Who cites it
107 citing papers in PubMed, 157 citations in OpenAlex.
- Predicting Toxicity and Response to Pembrolizumab Through Germline Genomic HLA Class 1 Analysis.JNCI cancer spectrum · 2021Trial
- Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis.bioRxiv : the preprint server for biology · 2026Article
- Tumor-derived type IX collagen regulates dormancy in triple-negative breast cancer cells.Scientific reports · 2026Article
- Peripheral blood transcriptional profiling predicts tumor subtype and neoadjuvant chemoimmunotherapy outcomes in human breast cancer.Science translational medicine · 2026Article
- A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.Cell reports. Medicine · 2026Article
- Integrative analysis of T cell subset-specific ICOS expression and tumor HLA class I/II expression in lung adenocarcinoma: implications for their interaction and clinical outcome.Cancer immunology, immunotherapy : CII · 2026Article
- Interferon-gamma-inducible protein 30 prevents IFN-γ-receptor 1 degradation to maintain PD-L1 and MHC-II levels in metastatic melanoma.Cell communication and signaling : CCS · 2026Article
- Dual role of IFNγ in reprogramming the undifferentiated pleomorphic sarcoma cell line JBT19 towards cytotoxic chemotherapy and antitumor immunity.Oncology letters · 2026Article
- Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Single-cell and bulk transcriptomic analyses define an IFI27-centered interferon-response epithelial state in bladder cancer and its transcriptional response to irradiation.Frontiers in cell and developmental biology · 2026Article
- A comprehensive review of mechanisms underlying resistance to immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Two subsets of regulatory CD8iScience · 2025Article
- Biological mechanism and immune response of MHC-II expression in tumor cells.Cancer biology & medicine · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations.Cancers · 2025Review
- Peripheral blood gene expression signatures of systemic immunity predict tumor microenvironment biology and therapeutic response in breast cancer.Research square · 2025Article
- Decoding MHC loss: Molecular mechanisms and implications for immune resistance in cancer.Clinical and translational medicine · 2025Review
- Emerging Immunotherapy Targets in Early Drug Development.International journal of molecular sciences · 2025Review
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Prognostic nutrition index reveals LAG3 in cytotoxic CD8+ T cells and MHC class II in gastric cancer cells.Cancer immunology, immunotherapy : CII · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 9 institutions in 4 countries.
Funding
Abstract
Immunotherapies targeting the PD-1 pathway produce durable responses in many cancers, but the tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II expression on tumor cells can predict response to anti-PD-1 therapy. We therefore sought to determine how MHC-II expression by tumor cells promotes PD-1 dependency. Using transcriptional profiling of anti-PD-1-treated patients, we identified unique patterns of immune activation in MHC-II+ tumors. In patients and preclinical models, MHC-II+ tumors recruited CD4+ T cells and developed dependency on PD-1 as well as Lag-3 (an MHC-II inhibitory receptor), which was upregulated in MHC-II+ tumors at acquired resistance to anti-PD-1. Finally, we identify enhanced expression of FCRL6, another MHC-II receptor expressed on NK and T cells, in the microenvironment of MHC-II+ tumors. We ascribe this to what we believe to be a novel inhibitory function of FCRL6 engagement, identifying it as an immunotherapy target. These data suggest a MHC-II-mediated context-dependent mechanism of adaptive resistance to PD-1-targeting immunotherapy.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.