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PMID: 31882943 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

High CD3 and ICOS and low TIM-3 expression predict favourable survival in resected oesophageal squamous cell carcinoma.

Scientific reports ·Vol. 9 ·No. 1 ·2019-00-27 ·Pages 20197

Hong MH, Shin SJ, Shin SK, Kim DJ, Zo JI, Shim YM, Lee SE, Cho BC, Park SY, Choi YL, Kim HR

Abstract

With the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3+ TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3+ TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.

MeSH Terms
Adult Aged Aged, 80 and over CD3 Complex/metabolism Carcinoma, Squamous Cell/metabolism,pathology,surgery Esophageal Neoplasms/metabolism,pathology,surgery Female Hepatitis A Virus Cellular Receptor 2/metabolism Humans Inducible T-Cell Co-Stimulator Protein/metabolism Male Middle Aged Prognosis Survival Rate
Chemicals
CD3 Complex HAVCR2 protein, human Hepatitis A Virus Cellular Receptor 2 ICOS protein, human Inducible T-Cell Co-Stimulator Protein
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Hong Min Hee ORCID
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Shin Su-Jin
Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Shin Sung Kwan ORCID
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Kim Dae Joon
Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
Zo Jae Ill
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Shim Young Mog
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee Seung Eun
Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.
Cho Byoung Chul
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Park Seong Yong
Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea. SYPARKCS@yuhs.ac.
Choi Yoon-La ORCID
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ylachoi@skku.edu.
Kim Hye Ryun ORCID
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. nobelg@yuhs.ac.
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Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
DOI
10.1038/s41598-019-56828-7
Email
syparkcs@yuhs.ac
ylachoi@skku.edu
nobelg@yuhs.ac
Published
2019-00-27
Epub
2019-00-27
Pages
20197
Language
English
Region
England
NLM ID
101563288
PMCID
PMC6934772
Subset
IM
External Links
PubMed source DOI: 10.1038/s41598-019-56828-7 PMC Full Text View journal details
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