Abstract 475: Preoperativechemoradiation increases levels of immune system modulators in tumor tissue in locally advanced rectal cancer

Abstract

Purpose: Neoadjuvant chemoradiation therapy (CRT) is a widely and effectively used preoperative treatment strategy in locally advanced rectal cancers. However, little research has been done to characterize the molecular changes caused by neoadjuvant CRT in these cancer tissues. The purpose of this study was to investigate the effects of preoperative CRT on tumor gene expression in Korean patients with colorectal cancer (CRC). Materials and methods: We included 11 paired human rectal cancer tissues before and after irradiation between August 2016 and December 2017, and performed RNA sequencing analysis. Principal component analysis of CRC demonstrated strong similarity in respective groups of CRC tissues before and after CRT from CRC patients at the transcriptome level. Results: Volcano plot filtering identified 3325 differentially expressed genes (DEGs) in CRC tissues after CRT, compared to CRC tissues before CRT. Gene set enrichment analysis with DEGs revealed 45 signaling pathways associated with down-regulated target genes, significantly including the mismatch repair signaling pathway. CRT significantly increased tumor mutation burden (TMB) in CRC tissues. Notably, preoperative CRT increased immune signature scores including interferon-gamma, immune cytolytic score, and immune signature. Conclusion: Neoadjuvant CRT modulates immune-related characteristics of CRC, including increasing TMB and various immune signature scores, suggesting that neoadjuvant CRT has potential to improve responsiveness to immunotherapy. Citation Format: SungUk Bae, Shin Kim, Hye Won Lee, Sang Jun Byun, Jee Young Park, Hyeonji Min. Preoperativechemoradiation increases levels of immune system modulators in tumor tissue in locally advanced rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 475.