title: Myeloid-derived suppressor cells and their role in CTLA-4 blockade therapy.
abstract: Immune checkpoints are a series of inhibitory pathways that are crucial for modulating the intensity and duration of immune response. Among these checkpoints, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) has been shown to be a key regulator of the early activation of naïve and memory T cells. Immune checkpoint blockade is emerging as one of the most promising therapeutic approaches directed toward the activation of the immune response against tumors. The first of these therapies that has been FDA approved is ipilimumab, a fully human monoclonal antibody that blocks CTLA-4. The in cis effects that CTLA-4 blockade has on T cells have been properly described, but there are still questions to be answered regarding the indirect or in trans effects. One of the alternative cellular populations that may play a role in the outcome of CTLA-4 blockade therapy is myeloid-derived suppressor cells (MDSCs), which have recently been associated with clinical outcome in advanced melanoma. In addition to this, MDSCs have been shown to be decreased in number and functional potential after treatment with ipilimumab. A better clarification of what effects CTLA-4 blockade may have on these cellular populations is likely to provide insights on possible predictive biomarkers for CTLA-4 blockade therapy.
authors: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, R08:01, 171 76, Stockholm, Sweden, yago.pico.de.coana@ki.se.
authors: Yago
authors: Y
authors: Pico de Coaña
authors: Giuseppe
authors: G
authors: Masucci
authors: Johan
authors: J
authors: Hansson
authors: Rolf
authors: R
authors: Kiessling
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D000074324:Ipilimumab; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab