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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 212; p. 108240
• Main Authors: Rodríguez-Rodríguez, Noé, Madera-Salcedo, Iris K., Bugarin-Estrada, Emmanuel, Sánchez-Miranda, Elizabeth, Torres-García, Diana, Cervantes-Torres, Jacquelynne, Fragoso, Gladis, Rosetti, Florencia, Crispín, José C., Sciutto, Edda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2020
• Subjects: CD8 T cell; GK-1; Melanoma; PD-1; CD8 T cell; GK-1; PD-1; Melanoma
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2019.07.006

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. •GK-1 improves the anti-tumor CD8 response.•GK-1 promotes IFN-γ production and inhibits PD-1 expression on CD8 T cells.•GK-1 abrogates tumor-induced upregulation of PD-L1 on dendritic cells.