ArticleJournal for immunotherapy of cancer2026
Modulating the tumor immune phenotypes by radiotherapy: formulating and validating the combination therapy of radiation, PD-L1, and TIM-3 blockade in colorectal cancer.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Immunotherapy Resistance in dMMR/MSI-H Colorectal Cancer: Unraveling Mechanisms and Exploring Overcoming Strategies.Journal of immunology research · 2026Review
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Authors and funding
14 authors.
Funding
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Abstract
backgroundMost colorectal cancers (CRCs) are mismatch repair-proficient (pMMR) and microsatellite stable (MSS), and they respond poorly to immune checkpoint inhibitors (ICIs). Radiotherapy (RT) can promote antitumor immunity but may also trigger adaptive immune suppression through checkpoint upregulation, providing a rationale for combination therapies.
methodsWe integrated transcriptomic analyses from The Cancer Genome Atlas and Gene Expression Omnibus cohorts-annotated for microsatellite instability (MSI)/MMR status-with single-cell RNA-sequencing data from the Human Colorectal Cancer Atlas. Mechanistic and translational experiments were conducted using CT26 (MSS/pMMR) and MC38 (microsatellite instability (MSI)-high/mismatch repair-deficient (dMMR)) mouse models, patient-derived organoid (PDO)-immune co-cultures, and clinical CRC specimens. Assessments included multicolor flow cytometry, immunohistochemistry/immunofluorescence, bulk RNA-sequencing, and immune profiling.
results
conclusionsThese findings identify TIM-3/PD-L1 as a context-dependent adaptive resistance axis following RT. The greatest incremental value of TIM-3 blockade was observed in MSS/pMMR settings, where RT more consistently increased PD-1 and TIM-3 co-expression on intratumoral CD8
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