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

Sci Rep. 2019 Dec 27;9(1):20197. doi: 10.1038/s41598-019-56828-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD3 Complex / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate

Substances

  • CD3 Complex
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein