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CCT2 Promotes Immune Escape in Colorectal Cancer by Regulating the JAK1-STAT3-PD-L1 Axis
Liqiang Gu1, Shaofei Li1, Yichao Tang1
1Department of Colorectal Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
Journal of Gastroenterology and Hepatology
|August 12, 2026
Summary
Chaperonin containing TCP1 subunit 2 (CCT2) promotes colorectal cancer immune evasion by upregulating programmed cell death ligand 1 (PD-L1) through the JAK1-STAT3 pathway. Targeting CCT2 may enhance colorectal cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Colorectal cancer (CRC) poses a significant global health challenge.
- Current immunotherapies, like immune checkpoint inhibitors, show limited efficacy in microsatellite-stable CRC.
- Understanding CRC immune evasion mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the molecular mechanisms behind colorectal cancer's immune evasion.
- To identify key molecular targets for improving CRC immunotherapy.
Main Methods:
- Bioinformatics and machine learning for target screening.
- RT-PCR, Western blot, ELISA, and various cell-based assays (EdU, TUNEL, Transwell, wound healing, LDH) for molecular and cellular analysis.
- In vivo studies using xenograft mouse models and immunohistochemistry for validation.
Main Results:
- CCT2 was identified as a core gene in CRC with significantly increased expression in tumor tissues.
- CCT2 knockdown suppressed CRC cell proliferation, invasion, and migration in vitro and in vivo.
- CCT2 expression positively correlated with PD-L1 levels in CRC patients.
- CCT2 knockdown enhanced CD8+ T cell activation and proinflammatory cytokine secretion by downregulating PD-L1 via the JAK1-STAT3 pathway.
Conclusions:
- Upregulated CCT2 drives colorectal cancer immune escape by modulating the JAK1-STAT3-PD-L1 axis.
- CCT2 represents a potential therapeutic target for enhancing colorectal cancer treatment.
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