The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway

Clin Immunol. 2020 Mar;212:108240. doi: 10.1016/j.clim.2019.07.006. Epub 2019 Jul 9.

Abstract

CD8 T cells can kill malignant cells in an antigen-specific manner. However, anti-tumoral responses are usually limited by suppressive factors that curb the effector responses of tumor-infiltrating CD8 T cells. Therapeutic strategies to overcome intra-tumoral T cell suppression, for example immune checkpoint inhibition, have been clinically effective in patients with cancer. Here, we provide data that demonstrates that GK-1, a peptide derived from the parasite Taenia crassiceps, promotes an anti-melanoma CD8 T cell response with heightened effector characteristics that leads to an increased amount of tumor-infiltrating CD44+ IFN-γ-producing CD8 T cells. The response induced by GK-1 was associated with a reduction in the expression of PD-1 and PD-L1 on tumor-infiltrating CD8 and dendritic cells, respectively, effects that led to a dramatic decrease in tumor burden. Our results suggest that the immunomodulatory properties of GK-1 may promote a CD8 T cell response that may be therapeutically useful in the setting of cancer.

Keywords: CD8 T cell; GK-1; Melanoma; PD-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B7-H1 Antigen / drug effects*
  • B7-H1 Antigen / immunology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Down-Regulation
  • Hyaluronan Receptors / immunology
  • Interferon-gamma / immunology
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Peptides, Cyclic / pharmacology*
  • Programmed Cell Death 1 Receptor / drug effects*
  • Programmed Cell Death 1 Receptor / immunology
  • Skin Neoplasms / immunology*
  • T-Lymphocytes / transplantation
  • Taenia
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • Hyaluronan Receptors
  • Peptides, Cyclic
  • Programmed Cell Death 1 Receptor
  • cyclo(cysteinyl-glycyl-aspargyl-seryl-aspargyl-prolyl-lysyl-seryl-cysteine)
  • Interferon-gamma