CD103阻滞剂影响口腔癌抗CTLA-4免疫治疗的效果。
CD103 blockade impair anti-CTLA-4 immunotherapy in oral cancer.
发表日期:2023 Mar
作者:
Yao Xiao, Liang Mao, Qi-Chao Yang, Shuo Wang, Zhi-Zhong Wu, Shu-Cheng Wan, Meng-Jie Zhang, Zhi-Jun Sun
来源:
ORAL ONCOLOGY
摘要:
CD103+CD8+T细胞是一种具有优异肿瘤杀伤能力的T细胞亚型,可以在多种癌症中对免疫检查点阻断治疗做出反应,但在口腔鳞癌中CD103+CD8+T细胞的表型、作用和分子机制还不清楚。本研究通过对人类口腔鳞癌组织微阵列进行多重免疫组化和活体内使用anti-CD103单克隆抗体(mAb)在4MOSC1移植瘤小鼠模型中进行CD103+CD8+T细胞渗透和细胞毒性的验证,揭示了CD103+CD8+T细胞的分布和表型。在人和动物的口腔鳞癌肿瘤内部区域中,大多数CD8+T细胞都是表达CD103的CD8+T细胞,这些细胞具有高水平的细胞毒素表达,其表达可以被CD103阻断。此外,联合使用anti-CD103 mAb和anti-CTLA-4 mAb可以降低免疫检查点阻断治疗效果。因此,CD103+CD8+T细胞是成年和人类口腔鳞癌中的主要肿瘤内亚群,具有显著的肿瘤内渗透和肿瘤杀伤特性,因此CD103+CD8+T细胞可能对口腔鳞癌的抗-CTLA-4免疫疗法至关重要。 版权©2023 Elsevier Ltd.版权所有。
CD103+CD8+T cells is a subtype of T cells with excellent tumor killing ability and it could response to immune checkpoint blockade therapy in several types of cancer, but the phenotype, role and molecular mechanism CD103+CD8+T cells in the OSCC still unclear.The distribution and phenotype of CD103+CD8+T cells were investigated by performing multiplexed immunohistochemistry on human OSCC tissue microarray and flow cytometric analysis of fresh OSCC tumor-infiltrating lymphocytes (TILs). By in vivo use of anti-CD103 monoclonal antibody (mAb) in the 4MOSC1 tumor-bearing mouse model, CD103+CD8+T cell infiltration and cytotoxicity was clarified.The majority of CD8+T cells in both human and animal OSCC intra-tumoral region were CD103+CD8+T cells with high expression levels of cytotoxic molecules, which can be impaired by CD103 blockade. In addition, combined use of anti-CD103 mAb with anti-CTLA-4 mAb displayed impaired immune checkpoint blockade therapy efficiency.CD103+CD8+T cells are the major intra-tumoral subset of CD8+T cells in both animal and human OSCC, and that CD103+CD8+T cells demonstrate remarkable tumor-infiltrating and tumor-killing properties, thereby CD103+CD8+T cells may critical for anti-CTLA-4 immunotherapy in OSCC.Copyright © 2023 Elsevier Ltd. All rights reserved.