Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors

Sci Rep. 2020 Mar 4;10(1):4064. doi: 10.1038/s41598-020-61053-8.

Abstract

Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed phenotypic and functional analyses of T cells in surgically resected TET tissues with a focus on the anti-tumor properties of T cells to TETs as a step towards establishing a rationale for immunotherapy for TETs. We examined T-cell profiles in surgically resected TET tissues, particularly CD4 and CD8 single-positive T cells, using flow cytometry. In the functional analysis of T cells in TETs, we investigated not only cytokine production by T cells, but also their cytotoxicity using bispecific T-cell engager technology. The cluster analysis of T-cell profiles based on flow cytometric data revealed that type B3 thymoma and thymic carcinoma (B3/C) belonged to the hot cluster characterized by a high proportion of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells. Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C. These results indicate the potential of immunotherapy for patients with B3/C.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Humans
  • Immunity, Cellular*
  • Immunotherapy*
  • Male
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / immunology*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / therapy*
  • Thymus Neoplasms / immunology*
  • Thymus Neoplasms / pathology
  • Thymus Neoplasms / therapy*

Supplementary concepts

  • Thymic epithelial tumor