ArticleCancer discovery2023
Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-Secreted Cytokines.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- PET imaging enables direct evaluation of ferroptosis in HCC synergistically induced by anti-PD-L1 and Olaparib.Experimental & molecular medicine · 2026Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- GPR183 potentiates CAR-T cell infiltration and antitumor immunity through a positive feedback loop involving the oxysterol 7α,25-OHC.Molecular cancer · 2026Article
- Machine learning-based identification of kbhb-affected tumor cell subsets as prognostic and therapeutic targets in breast cancer.Journal of translational medicine · 2025Article
- Exploring the role of neutrophil extracellular traps in colorectal cancer: Insights from single-cell sequencing.World journal of gastrointestinal oncology · 2025Review
- Decoding MHC loss: Molecular mechanisms and implications for immune resistance in cancer.Clinical and translational medicine · 2025Review
- PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.The Journal of experimental medicine · 2025Article
- Evolutionary trajectories of immune escape across cancers.bioRxiv : the preprint server for biology · 2025Article
- Overcoming Resistance Mechanisms to Melanoma Immunotherapy.American journal of clinical dermatology · 2025Review
- Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer.Cancer research · 2024Article
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Research progress and application of liver organoids for disease modeling and regenerative therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects.Molecular cancer · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I)-bound peptides, but this selection pressure favors outgrowth of MHC-I-deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I-deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I-deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified proapoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I-deficient tumor cells were efficiently cross-presented by dendritic cells, resulting in heightened tumor infiltration by IFNγ-and TNFα-producing T cells. Tumors with a substantial population of MHC-I-deficient cancer cells could be controlled by T cells when both pathways were targeted using genetic or pharmacologic approaches. SIGNIFICANCE: Tumor heterogeneity is a major barrier to immunotherapy. We show that MHC-I-deficient tumor cells are forced into apoptosis by T cell-derived cytokines when TNF signaling and autophagy pathways are targeted. This approach enables T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient tumor cells. This article is highlighted in the In This Issue feature, p. 1027.
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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.