ArticleCancer immunology research2022
BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Temporal and transcriptional programming of effector memory B cells shapes vaccine platform-dependent humoral immunity.iScience · 2026Article
- BHLHE40 as a transcriptional rheostat: decoding microenvironmental signals in context-dependent tumor plasticity.Science China. Life sciences · 2026Review
- Subclinical cholestasis is a hallmark of gut dysbiosis causing resistance to cancer immunotherapy.Cancer cell · 2026Article
- Functional Type I and Type II interferon crosstalk restricts progenitor exhausted CD8 T cells through spatial exclusion and checkpoint enforcement.bioRxiv : the preprint server for biology · 2026Article
- A comprehensive review of the emerging role of NRF3 in ovarian cancer tumorigenesis and progression.Journal of ovarian research · 2026Review
- A distinct subset of stem-cell memory is poised for the cytotoxicity program in CD4Science advances · 2026Article
- Evolving role of CD8Frontiers in immunology · 2026Review
- Article
- Research hotspots and frontiers in the tumor microenvironment of gastric cancer: a bibliometric review from 2005 to 2024.Translational cancer research · 2025Article
- CAR T cell engineering impacts antigen-independent activation and co-inhibition.Molecular therapy. Methods & clinical development · 2025Article
- The role of circadian genes in predicting immunotherapy response and survival outcomes in cancer patients.Discover oncology · 2025Article
- Bhlhe40 Coordinates T Cell Programs with Distinct CD4 and CD8 T Cell Requirements for Anti-PD-1 Versus Anti-CTLA-4.bioRxiv : the preprint server for biology · 2025Article
- Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.Science advances · 2025Article
- Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection.The Journal of experimental medicine · 2025Article
- Deciphering the role of histone modifications in memory and exhausted CD8 T cells.Scientific reports · 2025Article
- Role of CD4Journal of translational medicine · 2025Review
- Article
- Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy.Cell reports · 2024Article
- BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming.Functional & integrative genomics · 2024Article
- TMED inhibition suppresses cell surface PD-1 expression and overcomes T cell dysfunction.Journal for immunotherapy of cancer · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential ICT-induced immune cell remodeling. The BHLHE40-dependent gene expression changes indicated dysregulated metabolism, NF-κB signaling, and IFNγ response within certain subpopulations of CD4+ and CD8+ T cells. Intratumoral CD4+ and CD8+ T cells from BHLHE40-deficient mice exhibited higher expression of the inhibitory receptor gene Tigit and displayed alterations in expression of genes encoding chemokines/chemokine receptors and granzyme family members. Mice lacking BHLHE40 had reduced ICT-driven IFNγ production by CD4+ and CD8+ T cells and defects in ICT-induced remodeling of macrophages from a CX3CR1+CD206+ subpopulation to an iNOS+ subpopulation that is typically observed during effective ICT. Although both anti-PD-1 and anti-CTLA-4 ICT in BHLHE40-deficient mice led to the same outcome-tumor outgrowth-several BHLHE40-dependent alterations were specific to the ICT that was used. Our results reveal a crucial role for BHLHE40 in effective ICT and suggest that BHLHE40 may be a predictive or prognostic biomarker for ICT efficacy and a potential therapeutic target.
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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.