The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway
Por:
Rodriguez-Rodriguez, Noe, Madera-Salcedo, Iris K., Bugarin-Estrada, Emmanuel, Sanchez-Miranda, Elizabeth, Torres-Garcia, Diana, Cervantes-Torres, Jacquelynne, Fragoso, Gladis, Rosetti, Florencia, Crispin, Jose C., Sciutto, Edda
Publicada:
1 mar 2020
Resumen:
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-gamma-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 tumorinfiltrating 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.
Filiaciones:
Rodriguez-Rodriguez, Noe:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Av Univ 3000, Mexico City 04510, DF, Mexico
Madera-Salcedo, Iris K.:
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Bugarin-Estrada, Emmanuel:
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Sanchez-Miranda, Elizabeth:
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Torres-Garcia, Diana:
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Av Univ 3000, Mexico City 04510, DF, Mexico
Cervantes-Torres, Jacquelynne:
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Av Univ 3000, Mexico City 04510, DF, Mexico
Fragoso, Gladis:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Av Univ 3000, Mexico City 04510, DF, Mexico
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Rosetti, Florencia:
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Crispin, Jose C.:
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Inmunol & Reumatol, Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
Sciutto, Edda:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Av Univ 3000, Mexico City 04510, DF, Mexico
Departamento de Inmunologia, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
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