title: Immunotherapy in Sarcoma: Future Horizons.
abstract: Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. burgessma@upmc.edu.|Sarcoma Program, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Fifth Floor, Pittsburgh, PA, 15232, USA. burgessma@upmc.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Burgess
authors.affiliation: Medical Oncology, American Oncology Institute, Serilingampally, Hyderabad, TS, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Gorantla
authors.affiliation: Division of Musculoskeletal Oncology, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.|Sarcoma Program, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Fifth Floor, Pittsburgh, PA, 15232, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Weiss
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|Sarcoma Program, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Fifth Floor, Pittsburgh, PA, 15232, USA.
authors.forename: Hussein
authors.initials: H
authors.lastname: Tawbi
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000639:trends; D058990:Molecular Targeted Therapy / Q000639:trends*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012509:Sarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D061026:Programmed Cell Death 1 Receptor
keywords: Immune checkpoint blockade; Immunosurveillance; Immunotherapy; Programmed death-1 (PD-1); Soft tissue sarcoma; Tumor-infiltrating lymphocyte (TIL)