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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1486888
This article is part of the Research Topic Response/Resistance to PD-1 Axis Inhibitors: Focus on the Tumor Microenvironment View all 12 articles

PD-L2 Act as An Independent Immune Checkpoint in Colorectal Cancer Beyond PD-L1

Provisionally accepted
Lvyun Zhu Lvyun Zhu 1*Ying Qu Ying Qu 1Tong Shao Tong Shao 1Jingyu Kuang Jingyu Kuang 1Chuanyang Liu Chuanyang Liu 1Yingying Li Yingying Li 1Sujuan Zhang Sujuan Zhang 2Jingyang Wang Jingyang Wang 1Yu Liu Yu Liu 1Yanhua Qi Yanhua Qi 1Jiali Liu Jiali Liu 1Yanming Hu Yanming Hu 2Lingyun Zhu Lingyun Zhu 1Tao Hou Tao Hou 2*
  • 1 National University of Defense Technology, Changsha, Hunan Province, China
  • 2 Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

The final, formatted version of the article will be published soon.

    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.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. 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.

    Keywords: Immune checkpoint blockade, colorectal cancer, antitumor immunity, Therapeutic target, Tumor Microenvironment

    Received: 27 Aug 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Zhu, Qu, Shao, Kuang, Liu, Li, Zhang, Wang, Liu, Qi, Liu, Hu, Zhu and Hou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lvyun Zhu, National University of Defense Technology, Changsha, Hunan Province, China
    Tao Hou, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.