PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1
IntroductionImmunotherapy, 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 microe...
| 出版年: | Frontiers in Immunology |
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| 主要な著者: | , , , , , , , , , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Frontiers Media S.A.
2024-12-01
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| 主題: | |
| オンライン･アクセス: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1486888/full |
| _version_ | 1849524935115931648 |
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| author | Lvyun Zhu Ying Qu Junru Yang Tong Shao Jingyu Kuang Chuanyang Liu Yanhua Qi Ming Li Ming Li Yingying Li Sujuan Zhang Jingyang Wang Yu Liu Jiali Liu Yanming Hu Lingyun Zhu Tao Hou |
| author_facet | Lvyun Zhu Ying Qu Junru Yang Tong Shao Jingyu Kuang Chuanyang Liu Yanhua Qi Ming Li Ming Li Yingying Li Sujuan Zhang Jingyang Wang Yu Liu Jiali Liu Yanming Hu Lingyun Zhu Tao Hou |
| author_sort | Lvyun Zhu |
| collection | DOAJ |
| container_title | Frontiers in Immunology |
| description | IntroductionImmunotherapy, 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.MethodsWe 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.ResultsIn 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.DiscussionOur 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. |
| format | Article |
| id | doaj-art-178441b2aee5470e8fc91c2c5efeb0f1 |
| institution | Directory of Open Access Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| spelling | doaj-art-178441b2aee5470e8fc91c2c5efeb0f12025-08-20T02:51:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14868881486888PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1Lvyun Zhu0Ying Qu1Junru Yang2Tong Shao3Jingyu Kuang4Chuanyang Liu5Yanhua Qi6Ming Li7Ming Li8Yingying Li9Sujuan Zhang10Jingyang Wang11Yu Liu12Jiali Liu13Yanming Hu14Lingyun Zhu15Tao Hou16Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaLaboratory of Liquid Propellant Application Technology, Jiuquan Satellite Launch Centre, Jiuquan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, ChinaDepartment of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaIntroductionImmunotherapy, 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.MethodsWe 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.ResultsIn 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.DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1486888/fullimmune checkpoint blockadecolorectal cancerantitumor immunitytherapeutic targettumor microenvironment |
| spellingShingle | Lvyun Zhu Ying Qu Junru Yang Tong Shao Jingyu Kuang Chuanyang Liu Yanhua Qi Ming Li Ming Li Yingying Li Sujuan Zhang Jingyang Wang Yu Liu Jiali Liu Yanming Hu Lingyun Zhu Tao Hou PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 immune checkpoint blockade colorectal cancer antitumor immunity therapeutic target tumor microenvironment |
| title | PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 |
| title_full | PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 |
| title_fullStr | PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 |
| title_full_unstemmed | PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 |
| title_short | PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1 |
| title_sort | pd l2 act as an independent immune checkpoint in colorectal cancer beyond pd l1 |
| topic | immune checkpoint blockade colorectal cancer antitumor immunity therapeutic target tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1486888/full |
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