PT - JOURNAL ARTICLE AU - Xiaofang Xing AU - Jinyao Shi AU - Yongning Jia AU - Yunsheng Dou AU - Zhongwu Li AU - Bin Dong AU - Ting Guo AU - Xiaojing Cheng AU - Xiaomei Li AU - Hong Du AU - Ying Hu AU - Shuqin Jia AU - Jian Zhang AU - Ziyu Li AU - Jiafu Ji TI - Effect of neoadjuvant chemotherapy on the immune microenvironment in gastric cancer as determined by multiplex immunofluorescence and T cell receptor repertoire analysis AID - 10.1136/jitc-2021-003984 DP - 2022 Mar 01 TA - Journal for ImmunoTherapy of Cancer PG - e003984 VI - 10 IP - 3 4099 - http://jitc.bmj.com/content/10/3/e003984.short 4100 - http://jitc.bmj.com/content/10/3/e003984.full SO - J Immunother Cancer2022 Mar 01; 10 AB - Background The combination of immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced gastric cancer (GC). It is crucial to unravel chemotherapy-induced tumor microenvironment (TME) modulation and identify which immunotherapy would improve antitumor effect.Methods In this study, tumor-associated immune cells (TAICs) infiltration in residual tumor after neoadjuvant chemotherapy (NAC) together with 1075 cases of treatment-naïve GC patients was analyzed first. Then we performed multiplex fluorescence staining of a panel of immune markers (CD3, CD4, CD8, FOXP3 and PDL1) and T cell receptor β-chain sequencing to phenotype and enumerate T cell subpopulations and clonal expansion in paired GC samples (prechemotherapy and postchemotherapy) from another cohort of 30 cases of stage II/III GC patients.Results Infiltration of CD68+ macrophages in residual tumors after NAC was significantly decreased compared with treatment-naïve GC patients, while no significant difference observed with respect to other immune markers. In residual tumors, post-NAC CD8 +T cells and CD68+ macrophages levels were significantly associated with chemotherapy response. Post-NAC CD8+ T cell levels remained as an independent predictor for favorable prognosis. Furthermore, when comparing the paired samples before and after NAC from 30 cases of stage II/III GC patients, we found FOXP3+ regulatory T cells proportion significantly decreased after chemotherapy. Pre-NAC FOXP3+ T reg cells level was much richer in the response group and decreased more significantly in the stromal compartment. CD8+ cytotoxic T lymphocytes levels were elevated after chemotherapy, which was more significant in the group treated with XELOX regimen and in patients with better response, consistent with the TCR diversity elevation.Conclusions These findings have deepened our understanding of the immune modulating effect of chemotherapy and suggest that the immune profile of specimens after standard chemotherapy should be considered for the personalized immunotherapy to ultimately improve clinical outcome in patients with GC.The data are available from the corresponding author on reasonable request.