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Background: Immunotherapy exhibits promising clinical efficacy in treating unresectable esophageal cancer, and several studies have demonstrated that both comutations in DNA damage response (DDR) pathways and tumor immune microenvironment(TIME) could serve as potential biomarkers for immune checkpoint blockade (ICB) treatment. However, the associtation between DDR comutations and TIME remains unclear. Methods: Between April 2020 and September 2020, NGS and TIME analysis of tumor tissue from 22 patients with esophageal cancer were performed by 3D Medicines, Inc., a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. We retrospectively investigated the association between genomic alterations and immune microenvironment features. Among eight DDR pathways, comutations of check point factors(CPF) plus base excision repair(BER), homologous recombination repair(HRR), mismatch repair(MMR) or Fanconi anemia(FA) were defined as "DDR co-mut+", while mutation of CPF or comutations of CPF plus nucleotide excision repair (NER) were defined as “DDR co-mut-”. In addition, the relationship between comutations of DDR pathways and tumor mutational burden (TMB) was also analyzed. Results: 22 patients with esophageal cancer were included for analysis. 16 of 22 patients (72.7%) were male and the median age was 62 years old(range, 52 to 73 years). Based on the definition of DDR co-mut+ and DDR co-mut-, 13 patients were devided into DDR co-mut+ group, and 9 patients belonged to DDR co-mut- group. Gene alterations and TIME analysis revealed that patients with DDR co-mut+ showed a higher abundance of CD56dim natural killer cells in both tumor(p=0.0161) and stroma(p=0.028) compared with DDR co-mut- patients. No differences were observed in the densities of CD8+ T cells, M1-TAMs, and M2-TAMs between DDR co-mut+ and DDR co-mut- patients. TMB analysis displayed slightly higher in DDR co-mut+ group with no significant difference. Conclusions: Patients with DDR co-mut+ showed better infiltration of CD56dim NK cells in tumor and stroma in esophageal cancer. Combination of DDR comutations with TIME features may be a more promising biomarker to guide immunotherapy. Keywords: esophageal cancer; DNA damage response pathway; tumor immune microenvironment; tumor mutational burden Citation Format: Hao Chen, Xihua Xia, Junling Zhang, Yanan Chen, Mengli Huang. Characteristics of tumor immune microenvironment in patients carrying comutations of DNA damage response pathways in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5096. |
