Neoadjuvant PD-1 blockade plus chemotherapy induces a high pathological complete response rate and anti-tumor immune subsets in clinical stage III gastric cancer

作者：Xiaohuan Tang, Mengyuan Li, Xiaolong Wu, Ting Guo, Li Zhang, Lei Tang, Fangzhou Jia, Ying Hu, Yan Zhang, Xiaofang Xing, Fei Shan, Xiangyu Gao, Ziyu Li · 发表于：OncoImmunology · 年份：2022 · DOI：10.1080/2162402x.2022.2135819 · 被引用次数：41 · 研究领域：Gastric Cancer Management and Outcomes、Gastrointestinal Tumor Research and Treatment、Cancer Immunotherapy and Biomarkers

First-line PD-1 blockade plus chemotherapy significantly improves the survival benefits in late-stage gastric cancer (GC) patients. However, the pathological response rate and effects on the immune microenvironment of neoadjuvant PD-1 blockade plus chemotherapy in patients with cTNM-stage III GC remain to be elucidated. Patients with cTNM-stage III GC who underwent neoadjuvant PD-1 blockade plus chemotherapy and surgery were enrolled. Four in vivo models bearing GC were jointly established to investigate the specific roles of chemotherapy and PD-1 blockade for GC treatment. The tumor immune microenvironment was analyzed by hematoxylin and eosin (H&E) and IHC staining, multicolor flow cytometry and immunofluorescence. A total of 75 patients with cTNM-stage III (cT2-4N1-3M0) gastric cancer who received neoadjuvant PD-1 blockade plus chemotherapy (SOX/XELOX) were included in this study. After treatment, 21 (28.0%) and 57 (76.0%) patients achieved pathological complete response (pCR) and post-therapy pathological downstaging. Subgroup analyses revealed that patients with CPS >1 (32.6% vs 8.3%) and dMMR (35.7% vs 25.4%) subtype had better efficacy. Additionally, the resected specimens showed more anti-tumor immune infiltration indicating a response to neoadjuvant PD-1 blockade plus chemotherapy. Multicolor immunofluorescence and in vivo experiments on mouse models revealed that elevated M1/M2 ratio of macrophages, CD8 + T cells and plasma cells indicated effective response to trea...