A risk signature with inflammatory and immune cells infiltration predicts survival and efficiency of chemotherapy in gastric cancer

Int Immunopharmacol. 2021 Jul:96:107589. doi: 10.1016/j.intimp.2021.107589. Epub 2021 May 24.

Abstract

Objective: Tumor immune microenvironment biomarkers might add predictive value for outcomes. This study aimed to construct a risk signature with tumor infiltration immune and inflammatory cells to improve the prediction of survival.

Methods: A risk signature model in combination with CD66b + neutrophils, CD3+ T, CD8+ T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013.

Results: The high CD66b expression predicted the poor disease special survival (DSS) and inversely correlated with the CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort. This was comparable to the disease-free survival (DFS) findings observed in the validation cohort. Furthermore, a risk stratification was developed from the integration of CD66b + neutrophils and T immune cells. For DFS and DSS, both demonstrated the worse prognosis in the high-risk group, when compared to the low-risk group in both the training cohort and validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses, and this risk signature model increased the predictive accuracy and efficiency for post-operative relapses. Moreover, the high-risk group identified a subgroup of GC patients who tended not to benefit from the adjuvant chemotherapy.

Conclusions: The incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC and this risk stratification has potential for identifying the subgroup of GC patients who could benefit from adjuvant chemotherapy.

Keywords: Chemotherapy; Gastric cancer; Lymphocyte; Neutrophil; Risk signature; Survival.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / immunology
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Adhesion Molecules / metabolism
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • GPI-Linked Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Subsets
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Neoplasm Staging
  • Neutrophils / metabolism
  • Risk Factors
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / secondary
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Microenvironment / immunology*

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD8 Antigens
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins