Tumor-infiltrating CD8+ T cells in ALK-positive lung cancer are functionally impaired despite the absence of PD-L1 on tumor cells
Tumor-infiltrating CD8+ T cells in ALK-positive lung cancer are functionally impaired despite the absence of PD-L1 on tumor cells
复制标题
尽管肿瘤细胞上缺乏 PD-L1，但 ALK 阳性肺癌中的肿瘤浸润 CD8 T 细胞功能受损
DOI：
10.1016/j.lungcan.2020.10.009
复制
发表时间：
2020-12-01
期刊：
影响因子：
5.3
通讯作者：
Fu, Xiangning
中科院分区：
文献类型：
--
作者：
Zeng, Chenxi;Gao, Yi;Fu, Xiangning
Several lines of evidence have demonstrated that programmed cell death 1 (PD-1) inhibitors as monotherapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer have little clinical activity. The underlying mechanisms remain not understood. In this study, using immunohistochemistry and in situ RT-PCR assays, we examined the expression of programmed cell death ligand 1 (PD-L1), PD-1, CD8, and interferon gamma (IFN-gamma) in tumors. Both epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-positive tumors were associated with low or absent membrane PD-L1 expression. Interestingly, unlike EGFR-mutant tumors with few tumor-infiltrating CD8(+) T cells, a significant number of PD-1-positive CD8(+) T cells infiltrated the ALK-positive tumor bed; however, these cells did not express IFNG mRNA. These results demonstrate that the ALK-positive tumor microenvironment suppresses the immune function of tumor-infiltrating CD8(+) T cells through a PD-1/PD-L1-independent mechanism, which might lead to the inability of ALK-positive tumors to respond to PD-1/PD-L1-based immunotherapy.
