ArticleCell reports. Medicine2026
Cathepsin-D-mediated MHC class I degradation contributes to immune evasion in colorectal cancer.
Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
5 citing papers in PubMed.
- Periodontitis-Associated Circulating EVs Promote Colorectal Cancer Progression via Carnosine-Mediated Acidosis Adaptation.Cell proliferation · 2026Article
- Cathepsins as Core Players in Obesity Pathogenesis: Emerging Therapeutic Targets.Biomolecules · 2026Review
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- NLRC5 expression within tumor cells is critical to activate adaptive and innate antitumor immune responses.Immunotherapy advances · 2026Article
- Chemoresistance in the era of immunotherapy: challenges and novel combinatorial strategies for digestive system tumors.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microsatellite stable (MSS) colorectal cancer (CRC) is often considered a "cold" tumor with limited response to programmed death-1 (PD-1) antibody monotherapy. The mechanisms underlying its intrinsic resistance to immunotherapy remain unclear. Here, we show that cathepsin D (CTSD) is highly expressed in MSS CRC and contributes significantly to immunotherapy resistance. Mechanistically, CTSD, acting as a protease, interacts with the α2 domain of the major histocompatibility complex (MHC) class I via the light chain of its catalytic domain, promoting MHC class I degradation through lysosomal pathways and impairing its recycling to the cell surface. This mechanism shields tumor cells from cytotoxic T-cell-mediated killing and facilitates immune evasion. Notably, genetic deletion or pharmacological inhibition of CTSD using pepstatin A prevents immune escape and enhances anti-PD-1 efficacy. These findings identify CTSD as a key mediator of immune evasion in MSS CRC and support the development of a combination therapy comprising CTSD inhibition and anti-PD-1 immunotherapy.
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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 Socratic graph.