PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1.

Autor:	Zhu L; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Qu Y; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Yang J; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Shao T; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Kuang J; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Liu C; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Qi Y; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Li M; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China.; Laboratory of Liquid Propellant Application Technology, Jiuquan Satellite Launch Centre, Jiuquan, China., Li Y; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Zhang S; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Wang J; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Liu Y; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Liu J; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Hu Y; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Zhu L; Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China., Hou T; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Dec 02; Vol. 15, pp. 1486888. Date of Electronic Publication: 2024 Dec 02 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1486888
Abstrakt:	Introduction: Immunotherapy, especially immune checkpoint blockade (ICB), holds promise as a therapeutic strategy in colorectal cancer (CRC) by harnessing the patient's immune system to target malignant cells. Particularly, the PD-1/PD-L1 axis is widely recognized for its critical role in tumor microenvironment immunosuppression. Antibodies targeting PD-1 or PD-L1 have shown sustained efficacy against various cancers, including CRC. Nonetheless, many CRC patients exhibit limited responses to such immunotherapy, and the resistance mechanisms remain incompletely understood. Methods: We conducted experiments with C57BL/6 mice, and used the MC38 cell line for ICB treatment studies in syngeneic mouse models. Gene and protein analyses were performed using qPCR, Western Blot, and flow cytometry, with bioinformatics for clinical data survival analysis. Results: In this study, we reveal that targeting PD-L2 emerges as a complementary therapeutic strategy to PD-1/PD-L1 blockade in CRC. Although PD-L2 is also inducible by IFNγ, like PD-L1, it displays a unique spatial distribution within the tumor microenvironment, implying discrete roles in immune evasion. Additionally, we uncovered a significant correlation between PD-L1 and PD-L2 expression levels and the infiltration of various immune cells, encompassing multiple dendritic cell (DC) subtypes. This correlation implies an enhanced antigen presentation process that may be unleashed by blocking these two immune checkpoints. Discussion: Our results highlight the significance of PD-L2 as an essential immune checkpoint alongside PD-L1 and emphasize its potential as a target for bolstering antitumor immunity in colorectal cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Zhu, Qu, Yang, Shao, Kuang, Liu, Qi, Li, Li, Zhang, Wang, Liu, Liu, Hu, Zhu and Hou.)
Databáze:	MEDLINE
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