Cathepsin-D-mediated MHC class I degradation contributes to immune evasion in colorectal cancer.
1/5 보강
Microsatellite stable (MSS) colorectal cancer (CRC) is often considered a "cold" tumor with limited response to programmed death-1 (PD-1) antibody monotherapy.
APA
Zhan W, Fu Y, et al. (2026). Cathepsin-D-mediated MHC class I degradation contributes to immune evasion in colorectal cancer.. Cell reports. Medicine, 7(1), 102534. https://doi.org/10.1016/j.xcrm.2025.102534
MLA
Zhan W, et al.. "Cathepsin-D-mediated MHC class I degradation contributes to immune evasion in colorectal cancer.." Cell reports. Medicine, vol. 7, no. 1, 2026, pp. 102534.
PMID
41483803 ↗
Abstract 한글 요약
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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