Identification of the function of γδ1 T cells in the lung cancer microenvironments

Clin Transl Oncol. 2022 Jul;24(7):1365-1371. doi: 10.1007/s12094-022-02780-4. Epub 2022 Jan 29.

Abstract

Purpose: To investigate whether γδ1 T cells derived from lung cancer tissues have immunosuppressive function and to verify the mechanism of immunosuppressive effect.

Methods: Fresh lung cancer tissue samples were collected, some of them were prepared tissue sections, the others were isolated and amplified into TILs cells, γδ1 T cells were isolated from TILs cells by immunomagnetic beads kits, and then cloned and amplified. The immunomodulatory effects of γδ1 T cells on naive and effector CD4+ T cells were detected by immunohistochemistry, flow cytometry, CCK8, ELISA and transwell culture.

Results: A high proportion of γδ1 T cells was found in lung cancer tissues. The cultural supernatants of γδ1 T cells could inhibit the proliferation of naive CD4+ T cells and decrease the secretion level of IL-2 by effector CD4+ T cells. Further studies showed that the expression levels of IL-8, MIP-1α, MIP-1β and RANTES were higher than that of IFN-γ, GM-CSF and TNF-α, TNF-β, however, their neutralizing antibodies could not block the immunosuppressive activity of the supernatant.

Conclusion: γδ1 T cells play an negative immunoregulation function in lung cancer microenvironments, and have obvious immunosuppressive effects on proliferation and cytokine release of naive CD4+ T cells and effector CD4+ T cells. Preliminary evidence from this study suggests that the mechanism of immunosuppressive effects is mediated by the soluble factors in γδ1 T cell culture supernatants, but its exact molecular mechanism needs to be further explored.

Keywords: CD4+ T cells; Immunotherapy; Lung cancer; TILs cells; γδ1 T cells.

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Cytokines / metabolism
  • Humans
  • Lung
  • Lung Neoplasms* / metabolism
  • T-Lymphocytes* / metabolism
  • Tumor Microenvironment

Substances

  • Cytokines