Prognostic Significance of Tumour Infiltrating Lymphocytes in Canine Oral Malignant Melanoma Treated With Anti-Programmed Cell Death Ligand 1 (PD-L1) Antibody Therapy.

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy for canine oral malignant melanoma (OMM). However, only a subset of cases have shown clinical responses. Additionally, predictive biomarkers for the efficacy of ICIs in veterinary medicine are yet to be established. Tumour-infiltrating lymphocytes (TILs) are predictive biomarkers for ICI therapy in humans. In this study, we aimed to investigate the predictive utility of TILs for canine OMM treated with ICI therapy. Immunohistochemistry was performed on pre-treatment pathological tissues to detect cells positive for CD3 (pan-T cell marker), Granzyme B (cytotoxic T lymphocyte or natural killer cell marker) and Foxp3 (regulatory T cell marker). Further, we analysed the infiltration patterns of these cells and their prognostic utility for anti-programmed cell death ligand 1 (PD-L1) antibody therapy. There were variances in the infiltration levels of each TIL subset; further, we observed several TIL infiltration patterns in canine OMM. Survival analysis revealed that high infiltration of CD3and Granzyme Bcells was significantly associated with prolonged progression-free survival and overall survival. Furthermore, the immune cell composition ratio, which reflected the balance between cytotoxic and regulatory cells, was significantly associated with survival time. These findings suggest that canine OMM exhibits immunological phenotypes analogous to those observed in human cancers. Taken together, the TIL profile holds significant potential as a prognostic biomarker for canine OMM treated with anti-PD-L1 antibody therapy.