Abstract 625: Remodeling of the tumor microenvironment in esophageal squamous cell carcinoma by neoadjuvant immunochemotherapy and its impact on therapeutic efficacy

Abstract Background: Patients with local advanced esophageal squamous cell carcinoma (ESCC) benefited from neoadjuvant immunochemotherapy (NAI) with 22%-55% of complete pathological responses (pCR). While unpredicted therapeutic resistance hampered prognosis of these patients. Thus, this study aimed to investigate tumor microenvironment (TME) remodeling pre- and post-NAI identifying predictive biomarkers and potential targets for patients with resistance to NAI. Methods: 65 patients with locally advanced ESCC, who were treated with neoadjuvant anti-PD-1 antibody and platinum-based chemotherapy at the First Affiliated Hospital of Zhejiang University School of Medicine between November 2019 and June 2020, were included in this study. Genomic DNA and RNA from paired pre-and post-treatment FFPE samples were harvested and subjected to targeted DNA and RNA sequencing. Pre- and post- therapeutic microenvironment and immune cell infiltration were dynamically assessed based on RNA sequencing data. Results: 37 of 65 patients responded to NAI (TRG0-1), while 28 of 65 patients displayed unfavored response (TRG2-3). Comparative analysis of TME characteristics before and after NAI revealed that, in the TRG2-3 group, LRRC15+ CAFs, and fibroblasts were significantly upregulated, while CD4 T cells and endothelium cells exhibited downregulation. Especially, TIGIT tended to be upregulated after NAI in the TRG 2-3 group. In the TRG0-1 group, significant upregulation of activated B cells, T-cells, myeloid dendritic cells, together with notable downregulations of immune suppressive features like Type 2 T helper cells, Tregs and LRRC15+ CAFs were observed in post-treatment samples. Conclusions: Our study indicates the dynamic remodeling of TME during-NAI treatment might influence therapeutic efficacy and disclose potentially targetable resistant mechanisms. These preliminary findings pave the way for further validation through prospective clinical studies. Citation Format: Rusidanmu Aizemaiti, Huifang Zhang, Changbin Zhu, Kun Zhou, Tao Hu, Shuang Lin, Xiao Teng, Jin Wang, Xing Li, Peng Ye. Remodeling of the tumor microenvironment in esophageal squamous cell carcinoma by neoadjuvant immunochemotherapy and its impact on therapeutic efficacy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 625.