Immunological impact of chemotherapy on the tumor microenvironment in gastric cancer

J Surg Oncol. 2021 May;123(8):1708-1715. doi: 10.1002/jso.26449. Epub 2021 Mar 8.

Abstract

Objective: This study aimed to investigate alterations in pre- and post-neoadjuvant chemotherapy (NACT) tumor-infiltrating immune cells and subsequent evaluation of the predictive and prognostic value of these changes in gastric cancer (GC).

Methods: Fifty patients with GC underwent three cycles of S-1 and oxaliplatin (SOX regimen)-NACT. Paired samples from tumor lesions before and after NACT were available for all patients participating in the study. Immunohistochemistry was performed for T cell subsets (CD3+ and CD8+ ) and macrophages (CD68+ and CD163+ ).

Results: After NACT, the average expression levels of CD3, CD8, CD68, and CD163 were significantly increased (p < .001). However, neither expression levels pre- nor post-chemotherapy correlated with treatment response. Multivariate Cox regression analysis demonstrated that upregulation of CD8/CD3 levels (hazard ratio [HR] = 0.117; 95% confidence interval [CI] = 0.031-0.446; p = 0.002) and CD163 levels after chemotherapy (HR = 2.258; 95% CI = 1.047-4.867; p = 0.038) were independent prognostic factors of overall survival.

Conclusion: Chemotherapy in GC is useful to induce CD3+ and CD8+ T lymphocytes as well as CD68+ and CD163+ macrophages in the tumor microenvironment in combination with its direct cytotoxic effects. These results indicate that chemotherapy may play a role in tumor immune microenvironment remodeling.

Keywords: chemotherapy; gastric cancer; tumor-associated macrophage; tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Oxaliplatin / therapeutic use
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Microenvironment*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Oxaliplatin