한빛사논문
- 조회968
Ryul Kim1#, Minae An2#, Hyuk Lee3#, Arnav Mehta4,5,6#, You Jeong Heo2, KyoungMee Kim7, Song-Yi Lee1, Jeonghyeon Moon8, Seung Tae Kim1, Byung-Hoon Min3, Tae Jun Kim3, Sun Young Rha9, Won Ki Kang1, Woong-Yang Park8,10**, Samuel J. Klempner5,11**, and Jeeyun Lee1,12**
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea 3Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4The Broad Institute of MIT and Harvard, Cambridge, MA, USA 5Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA 6Dana-Farber Cancer Institute, Boston, MA, USA 7Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 8Geninus Inc, Seoul, Korea 9Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. 10Samsung Genome Institute, Samsung Medical Center, Seoul, Korea 11Harvard Medical School, Boston, MA, USA 12Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Korea
#Co-first authors equally contributed: Ryul Kim, Minae An, Hyuk Lee, Arnav Mehta
**Co-CORRESPONDENCES TO Woong-Yang Park, MD, Samuel J. Klempner, MD, Jeeyun Lee, MD
Abstract
Chemotherapy is ubiquitous in frontline treatment of advanced gastric cancer, yet responses are heterogeneous, and little is known about mediators of chemotherapy (CTX) response. To move forward, understanding the effects of standard CTX on the tumor and immune microenvironment (TME) is needed. Coupling whole exome sequencing, bulk RNA and single-cell transcriptomics from paired pre- and on-treatment samples in treatment naive HER2-positive and HER2-negative gastric cancer patients, we define features associated with response to platinum-based CTX. Response was associated with on-treatment TME remodeling including NK-cell recruitment, decreased tumor-associated macrophages, M1-macrophage repolarization and increased effector T-cell infiltration. Among CTX non-responders, we observed low/absent PD-L1 expression or modulation, on-treatment increases in Wnt-signaling, B-cell infiltration and LAG-3 expressing T-cells coupled to an exodus of dendritic cells. We did not observe significant genomic changes in early on-treatment sampling. We provide a map of on-treatment TME modulation with standard CTX and nominate candidate future approaches.
논문정보
- Research article
- 2021년 12월 (BRIC 등록일 2021-12-28)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
