Vascular Normalization Was Associated with Colorectal Tumor Regression upon Anti-PD-L1 Combinational Therapy. (17th March 2023)

• Record Type: Journal Article
• Authors: Zhang, Yan; Gao, Jiayan; He, Yan; Qi, Ziwei; Qian, Long; Chen, Wanpei; Xu, Haiyan; Yue, Yanhua; Mao, Xunyuan; Guo, Shuxin; Zhou, Yan; Zhou, Shuru; Qin, Songbing; Zhang, Xueguang; Huang, Yuhui
• Other Names: Fernandes Elizabeth Soares Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2023(2023)
• Publication Date: 2023-03-17
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2023/5867047
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Anti-PD-L1 therapy exhibits durable efficacy, but only in a small fraction of cancer patients. The immunosuppressive tumor microenvironment (TME) is a crucial obstacle that impedes cancer immunotherapy. Here, we found that anti-PD-L1 therapy coupled with CD4 + T cell depletion induced colorectal tumor regression and vascular normalization, while monotherapy only retarded tumor growth without affecting the tumor vasculature. Moreover, simultaneous PD-L1 blockade and CD4 + T cell depletion eradicated intratumoral PD-L1 + lymphoid and myeloid cell populations, while additively elevating the proportions of CD44 + CD69 + CD8 +, central memory CD44 + CD62L + CD8 +, and effector memory CD44 + CD62L - CD8 + T cells, suggesting a reduction in immunosuppressive cell populations and the activation of CD8 + T cells in the TME. Moreover, anti-PD-L1 therapy reduced the proportions of intratumoral PD-L1 + immune cells and suppressed tumor growth in a CD8 + T cell dependent manner. Together, these results suggest that anti-PD-L1 therapy induces tumor vascular normalization and colorectal tumor regression via CD8 + T cells, which is antagonized by CD4 + T cells. Our findings unveil the positive correlation of tumor regression and vascular normalization in colorectal tumor models upon anti-PD-L1 therapy, providing a potential new strategy to improve its efficacy.