Immune effector cells, including cytotoxic T lymphocytes (CTLs) play essential roles in eliminating cancer cells. However, their functionality is often compromised, even when they infiltrate the tumor microenvironment (TME) or are transferred to cancer patients adoptively. In this study, we focused on galectin 9 (G9), an inhibitory ligand that we observed to be predominately positioned on the plasma membrane and readily interacts with CD8?+?CTL in the TME of nasopharyngeal carcinoma (NPC). We discovered that cell-cell contact between activated effector CTLs and target tumor cells (TarTC) with G9 overexpression led to cellular death defects. Despite the formation of CTL-TarTC conjugates, there is no impact on the cell number nor viability of CTL, and the release of cytolytic content and associated activity were not completely abrogated. Instead, this interaction promoted autophagy and restricted necrosis in the TarTC. Furthermore, reducing G9 expression in tumor cells enhanced the suppr...
| Authors | Kam, NW; Lau, CY; Lau, JYH; Dai, X; Liang, Y; Lai, SPH; Chung, MKY; Yu, VZ; Qiu, W; Yang, M; Smith, C; Khanna, R; Ng, KM; Dai, W; Che, CM; Lee, VH; Kwong, DLW |
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| Journal | Cellular & Molecular Immunology |
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| Date | 5/03/2025 |
| Grant ID | 06172156 | Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF); 06172156 | Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF); 06172156 | Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF) |
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| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41423-024-01253-8 |