The role of αβ T-cells in spontaneous regression of melanoma tumors in swine

Abstract

Using a porcine model, we describe Melanoma-Associated CD4⁺CD8^hi T-lymphocytes (MATL) in peripheral blood that increase during melanoma regression. These MATL possess the CD4⁺CD8^hi phenotype and they have their direct counterparts in Tumor Infiltrating Lymphocytes (TIL) isolated from melanoma loci. Both MATL and CD4⁺CD8^hi TIL have a similar expression of selected markers indicating that they represent effector/memory αβ T-cell subset. Moreover, although TIL also contain CD4^-CD8⁺ T-cells, only CD4⁺CD8^hi TIL expand during melanoma regression. Importantly, TIL isolated from different pigs and different melanoma loci among the same pig have similar composition of CD4/CD8 subsets, indicating that the composition of the MATL and TIL compartment is identical. Analysis of sorted cells from regressing pigs revealed a unique MATL subpopulation with mono-specific T-cell receptor that was further analyzed by sequencing. These results indicate that pigs regressing melanomas possess a characteristic population of recirculating T-cells playing a role in tumor control and regression.

Keywords: Cell surface molecules; Lymphocyte subpopulations; Melanoma; Porcine immune system; Tumor regression; αβ T-cells.