김승태 (성균관대학교 의과대학, 삼성서울병원)

한빛사논문

조회214

성균관대학교 의과대학, 삼성서울병원

CV File 121 kb

Cancer Discov., Feb 06 2024, | https://doi.org/10.1158/2159-8290.CD-23-0857 Early immune remodeling steers clinical response to frontline chemoimmunotherapy in advanced gastric cancer

Minae An ^1,#, Arnav Mehta ^2,3,4,#, Byung Hoon Min ^5,#, You Jeong Heo ^6,#, Samuel J. Wright ², Milan Parikh ^2,3, Lynn Bi ^2,3, Hyuk Lee ⁵, Tae Jun Kim ⁵, Song-Yi Lee ⁷, Jeonghyeon Moon ⁸, Ryan J. Park ^2,9, Matthew R. Strickland ^3,4, Woong-Yang Park¹⁰, Won Ki Kang ⁷, Kyoung-Mee Kim ¹¹, Seung Tae Kim ^7,*, Samuel J. Klempner ^3,4,*, Jeeyun Lee ^7,*

¹Experimental Therapeutics Development Center, Samsung Medical Center, Seoul, Korea
²The Broad Institute of MIT and Harvard, Cambridge, MA, USA
³Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA
⁴Harvard Medical School, Boston, MA, USA
⁵Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea ⁶Neocella, Inc. Irvine, CA, USA
⁷Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
⁸Departments of Neurology and Immunology, Yale School of Medicine, New Haven, CT, USA
⁹Division of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
¹⁰Geninus Inc, Seoul, Korea
¹¹Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

^#Co-first author, equal contribution
^*Corresponding authors: correspondence to Seung Tae Kim, Samuel J. Klempner or Jeeyun Lee

Abstract

Adding anti-PD1 to 5-FU/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy we conducted a phase II frontline trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab we transcriptionally profiled 358,067 single cells to identify evolving multicellular TME networks. Chemotherapy induced early on-treatment multicellular hubs with tumor-reactive T-cell and M1-like macrophage interactions in slow progressors. Faster progression featured increased MUC5A and MSLN containing treatment-resistance programs in tumor cells and M2-like macrophages with immunosuppressive stromal interactions. After pembrolizumab we observed increased CD8 T-cell infiltration and development of an immunity hub involving tumor-reactive CXCL13 T-cell program and epithelial interferon-stimulated gene programs. Strategies to drive increases in anti-tumor immune hub formation could expand the portion of patients benefiting from anti-PD1 approaches.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-15)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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