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

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

Publication date: Jul 09, 2019

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.

Rodr’iguez-Rodr’iguez, N., Madera-Salcedo, I.K., Bugarin-Estrada, E., S’anchez-Miranda, E., Torres-Garc’ia, D., Cervantes-Torres, J., Fragoso, G., Rosetti, F., Crisp’in, J.C., and Sciutto, E. The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway. 23356. 2019 Clin Immunol.

Concepts Keywords
Antigen TIGIT
Cancer LAG3
CD44 Immunotherapy
CD8 Immune checkpoint
Dendritic Cells Clinical medicine
Downregulation Medicine
GK Immune system
Helminth Medical specialties
Immunomodulatory Effector tumor
Malignant Dramatic decrease tumor
Melanoma Anti melanoma CD8
Parasite PD L1 tumor
Peptide Amount tumor
Tumor

Semantics

Type Source Name
gene UNIPROT CD8A
gene UNIPROT SMIM10L2A
gene UNIPROT RPL17
gene UNIPROT PDCD1
gene UNIPROT CD274
disease MESH tumor
disease DOID cancer
disease MESH melanoma
disease DOID melanoma
pathway BSID Melanoma
gene UNIPROT CD44
gene UNIPROT SMIM10L2B

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