Cisplatin-based chemoradiation decreases telomerase-specific CD4 TH1 response but increases immune suppressive cells in peripheral blood

BMC Immunol. 2021 Jun 18;22(1):38. doi: 10.1186/s12865-021-00429-5.

Abstract

Background: The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. Here, we investigated the systemic immune effects of CRT in patients with lung or head and neck cancer.

Materials and methods: Peripheral blood mononuclear cells were collected at baseline and 1 month after treatment from blood samples of 29 patients treated with cisplatin-based chemoradiotherapy for lung or head and neck cancer. Circulating anti-tumor Th1 response was assessed by the ELISpot assay using a mixture of human leucocyte antigen (HLA) class II restricted peptides derived from telomerase (TERT). Phenotyping of circulating immunosuppressive cells (Treg and MDSC) was performed by flow cytometry.

Results: A significant increase of circulating Treg was observed in 60% of patients after CRT The mean rate of Treg was 3.1% versus 4.9% at baseline and after CRT respectively, p = 0.0015). However, there was a no significant increase of MDSC rate after CRT. In contrast, a decrease of tumor-specific Th1 response was documented in 7 out of 10 evaluated patients. We found high frequency of pre-existing tumor-specific Th1 response among patients with objective response after CRT compared to non-responders.

Conclusion: Cisplatin-based CRT promotes expansion of Treg and decrease of circulating anti-tumor Th1 response in peripheral blood. The balance towards a sustained specific anti-tumor T-cell response appears to be associated with response to CRT.

Keywords: Chemoradiation; Immune suppressive cells; Tumor-specific T cell response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD4 Antigens / metabolism
  • Cisplatin / therapeutic use
  • Enzyme-Linked Immunospot Assay
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immune Tolerance
  • Immunophenotyping
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Neoadjuvant Therapy / methods*
  • Peptides / genetics
  • Peptides / immunology
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes, Regulatory / immunology*
  • Telomerase / genetics
  • Telomerase / immunology
  • Th1 Cells / immunology*

Substances

  • Antigens, Neoplasm
  • CD4 Antigens
  • Peptides
  • Telomerase
  • Cisplatin