AUTHOR=Elia Angela Rita , Caputo Sara , Bellone Matteo 

TITLE=Immune Checkpoint-Mediated Interactions Between Cancer and Immune Cells in Prostate Adenocarcinoma and Melanoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01786

DOI=10.3389/fimmu.2018.01786

ISSN=1664-3224

ABSTRACT=Prostate adenocarcinoma (PCa) and melanoma are paradigmatic examples of tumors that are either poorly or highly sensitive to therapies based on monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). Yet, approximately 40% of melanoma patients are resistant or acquire resistance to ICB. What characterize the microenvironment of PCa and ICB-resistant melanoma are a scanty cytotoxic T cell infiltrate and a strong immune suppression, respectively. Here we compare the tumor microenvironment in these two subgroups of cancer patients, focusing on some among the most represented immune checkpoint molecules: cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), program death-1 (PD-1), Lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). We also report on several examples of crosstalk between cancer and immune cells that are mediated by inhibitory immune checkpoints, and identify promising strategies aimed at overcoming ICB-resistance both in PCa and melanoma.