Liver metastases develop in 20% uveal melanoma (UM) patients. Only 10% of these patients are eligible for hepatic resection, which can improve patient outcome. In the absence of proven standard of care, anti-checkpoint therapies have been tried with only anecdotal tumor regression. The characterization of the immune response in UM metastases may provide information to optimize immunotherapies in this disease.
Herein, we studied the lymphocytes present in the metastases as well as in the juxta-tumoral liver. We also characterized the circulating lymphocytes in peripheral blood (PBL) before and after hepatic metastasectomy. We studied 30 UM patients whose primary tumor had been treated by enucleation (14) or radiotherapy (16). Infiltrating lymphocytes were isolated from liver samples by enzymatic digestion. Both liver lymphocytes and PBL were analyzed by flow cytometry using a panel of 13 antibodies.
CD8+ T-cells were in similar proportion in juxta-tumoral liver and metastases. In contrast, the proportion of CD4+ T-cells, notably the Tregs and the chronically activated effector CD4 T-cell subsets were increased in the metastases. MAIT cells were abundant in the healthy liver but were underrepresented in the metastases. NKT cells, which are rare in the blood, represented up to 4% of the lymphocytes in juxta-tumoral and metastatic liver.
Thus, liver metastases are infiltrated with effector CD4 T-cells that dilute out the resident MAIT cells. No obvious change in the phenotype and proportion of CD8 T-cells was observed. The increased proportion of Treg may be implicated in the absence of productive anti-tumor immune response in UM patients.
Institut Curie, Université René Descartes Paris V