title: Prospective immunotherapies in childhood sarcomas: PD1/PDL1 blockade in combination with tumor vaccines.
abstract: Progress has slowed substantially in improving survival rates for pediatric sarcomas, particularly in refractory and metastatic disease. Significant progress has been made in the field of tumor vaccines for such malignancies, which target established tumor antigens. While tumor vaccines have demonstrated safety and improved survival rates, they are inadequate in mediating the regression of established tumor masses and metastases. Programmed cell death ligand 1 (PDL1) is a cell-surface protein induced in a number of adult malignancies. By acting on the corresponding T-cell receptor PD1, PDL1 is able to suppress cytotoxic T-cell-mediated tumor responses. Recent therapeutics blocking this interaction have shown promise in various adult cancers by restoring a functional T-cell response and by directing this response toward an activated, rather than regulatory, T-cell phenotype. We shall discuss the current state of tumor vaccines targeting pediatric sarcomas, review PD1-PDL1 interactions and current therapies targeting these interactions in adult malignancies, and discuss recent studies in which tumor vaccines, combined with PDL1 blockades, produced superior tumor regression compared with the vaccine alone. These studies provide a compelling case for investigation of PDL1 expression and its inhibition in pediatric sarcomas, while continuing to utilize tumor vaccines in tandem to achieve superior clinical outcomes.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California-Los Angeles, Los Angeles, California.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Nowicki
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California-Los Angeles, Los Angeles, California.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Anderson
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California-Los Angeles, Los Angeles, California.|UCLA's Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
mesh_terms: D000328:Adult; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology; D002648:Child; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D009362:Neoplasm Metastasis; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012509:Sarcoma / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D019496:Cancer Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell