한빛사논문
- 조회327
Incheol Seo,1 Hye Won Lee,2,3 Sang Jun Byun,4 Jee Young Park,2,5 Hyeonji Min,5 Sung Hwan Lee,6,7 Ju-Seog Lee,7 Shin Kim,5,7,8 Sung Uk Bae8,9
1Department of Microbiology, Dongguk University College of Medicine, Gyeongju, Gyeongsangbuk-do, Korea (the Republic of)
2Department of Pathology, Keimyung University Dongsan Medical Center, Daegu, Korea (the Republic of)
3Institute for Cancer Research, Keimyung University, Daegu, Korea (the Republic of)
4Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
5Department of Immunology, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
6Department of Surgery, CHA University - Bundang Campus, Seongnam, Gyeonggido, Korea (the Republic of)
7Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
8Institute of Medical Science & Institute for Cancer Research, Keimyung University, Daegu, Korea (the Republic of)
9Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea (the Republic of)
IS and HWL contributed equally.
Correspondence to Professor Shin Kim, Professor Sung Uk Bae
Abstract
Background: Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.
Methods: We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.
Results: Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.
Conclusions: Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
논문정보
- Research article
- 2021년 03월 (BRIC 등록일 2024-01-11)
- 국내(교신)+국외 연구진
- 의약학 > 면역의학
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