M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell...

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Vydáno v:	Oncoimmunology Ročník 10; číslo 1; s. 1862520
Hlavní autoři:	Zhao, Rui, Wan, Qianyi, Wang, Yong, Wu, Yutao, Xiao, Shuomeng, Li, Qiqi, Shen, Xiaoding, Zhuang, Wen, Zhou, Yong, Xia, Lin, Song, Yinghan, Chen, Yi, Yang, Hanshuo, Wu, Xiaoting
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Taylor & Francis 01.01.2021 Taylor & Francis Group
Témata:	gastric cancer Original Research PD-L1/PD-1 blockades Tumor-associated macrophages gastric cancer PD-L1/PD-1 blockades Tumor-associated macrophages
ISSN:	2162-402X, 2162-4011, 2162-402X
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Shrnutí:	The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68 + CD163 − macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68 + CD163 − macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68 + CD163 − macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Rui Zhao, Qianyi Wan, and Yong Wang contributed equally to this study.
ISSN:	2162-402X 2162-4011 2162-402X
DOI:	10.1080/2162402X.2020.1862520