Hirsutella sinensis Inhibits Lewis Lung Cancer via Tumor Microenvironment Effector T Cells in Mice

Am J Chin Med. 2018;46(4):911-922. doi: 10.1142/S0192415X18500489. Epub 2018 May 13.

Abstract

Hirsutella sinensis fungus (HSF) is an artificial substitute of the well-known medicine Cordyceps sinensis with similar beneficial effects in humans. We previously found that HSF can regulate immune function and inhibit tumor growth; however, the mechanisms involved in these effects were still unclear. Accordingly, in this study, we investigated the effects of HSF on immune cell subsets in the tumor microenvironment in mice. The results showed that HSF inhibited Lewis lung cancer growth, alleviated abnormalities in routine blood tests, and enhanced tumor-infiltrating T cells, particularly the proportion of effector CD8[Formula: see text] T cells. In addition, HSF also ameliorated the immune-suppressive microenvironment and decreased the proportions of regulatory T cell and myeloid-derived suppressor cell populations. To confirm the effects of HSF on promotion of effector CD8[Formula: see text] T-cell production, we further evaluated changes in postoperative metastasis following treatment with HSF. Indeed, orthotopic lung metastasis was significantly suppressed, and survival times were increased in HSF-treated mice. Taken together, our findings suggested that HSF inhibited Lewis lung cancer by enhancing the population of effective CD8[Formula: see text] T cells.

Keywords: Breast Cancer Metastasis; Hirsutella sinensis; Immunotherapy; Orthotopic Mouse Model.

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Ascomycota / chemistry*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / pathology*
  • Cordyceps
  • Disease Models, Animal
  • Immune Tolerance / drug effects
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology*
  • Lymphocyte Subsets / immunology
  • Male
  • Mice, Inbred C57BL
  • Myeloid-Derived Suppressor Cells / immunology
  • Myeloid-Derived Suppressor Cells / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Tumor Cells, Cultured
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents