| Title: |
CEBPB Expression in Tumor Cells Drives Immune Evasion in Colorectal Cancer via CTLA4 Up-regulation in T Cells |
| Authors: |
Hye Jeong Yun; Chan Ho Park; Dahye Yun; Hye-Ri Shin; Jeong Dong Lee; Changhee Park; Kiyeon Kim; Heejun Shim; Hyejin Sim; Se Min Kim; Min Jung Kim; Ji Won Park; Seung-Bum Ryoo; Yoojoo Lim; Seung-Yong Jeong; Kyu Joo Park; Tae-You Kim; Junil Kim; Jae-Kyung Won; Sae-Won Han |
| Source: |
Cancer Communications, Vol 46 (2026) |
| Publisher Information: |
Wiley |
| Publication Year: |
2026 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282 |
| Description: |
Background: Immune checkpoint inhibitors are ineffective in the majority of colorectal cancers (CRCs) that are microsatellite stable. However, the underlying reasons for their unresponsiveness and mechanisms of immune evasion are poorly understood. In the present study, we aimed to elucidate the mechanisms underlying the immune evasion driven by CRC cells. Methods: We performed single-cell RNA sequencing of tumor tissues from 30 CRC patients and syngeneic mice implanted with transformation-related protein 53 (Trp53) knockout CT26 cells. Gene expression and correlations of individual tumor microenvironment (TME) components were analyzed, and their functional significance was investigated using syngeneic mouse models and cell line co-culture experiments. Results: CCAAT enhancer-binding protein beta (CEBPB) expression was increased in tumor protein 53 (TP53)-mutated CRCs. We confirmed that wild-type TP53 negatively regulated CEBPB expression in CRC cell lines. CEBPB expression was associated with decreased intratumoral T cell infiltration and negatively impacted survival in CRC patients. In the intercellular correlation analysis of gene expression, tumor epithelial cell CEBPB expression was significantly correlated with cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in T cells, especially in regulatory and exhausted T cells. Cebpb overexpression promoted tumor growth in the immunocompetent syngeneic mouse models, which was accompanied by increased CTLA-4 expression in tumor-infiltrating CD4+ T cells. In vitro co-culture experiments also showed that tumor cell CEBPB overexpression increased CTLA4 in T cells. Conclusions: Tumor cell CEBPB expression, up-regulated by TP53 mutation, can increase CTLA4 expression in T cells and negatively affect patient outcomes. These findings suggested a central role of tumor cell CEBPB in shaping an immunosuppressive TME. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doaj.org/toc/2523-3548; https://doaj.org/article/17ca98ff1ebb460dbe2ee7ddcbaa317a |
| DOI: |
10.34133/cancomm.0013 |
| Availability: |
https://doi.org/10.34133/cancomm.0013; https://doaj.org/article/17ca98ff1ebb460dbe2ee7ddcbaa317a |
| Accession Number: |
edsbas.4DA3D4DC |
| Database: |
BASE |