title: The future of immunotherapy for sarcoma.
abstract: The use of immunotherapeutic challenges for sarcoma has a long history. Despite the existence of objective responses, immunotherapy has been overshadowed by the results of chemotherapy, especially for osteosarcoma. However, the prognosis for non-responders to chemotherapy is still poor and immunotherapy is now focused on again.
  
  
  
  We reviewed the following types of clinical trials of immunotherapy for sarcoma: (i) vaccination with autologous tumor cells, (ii) vaccination with peptides derived from tumor-associated antigens, (iii) adoptive cell transfer using engineered T cells expressing T cell receptor directed at NY-ESO-1 and (iv) immune checkpoint inhibitors targeting CTLA-4 and PD1/PDL1.
  
  
  
  The immunogenicity of sarcoma might be lower than that of melanoma. Patients with small lesions who have not received any chemotherapy are good candidates for peptide-based immunotherapy. Combining peptide vaccination and immune checkpoint inhibitors is an attractive option, and long-lived memory T cells are attracting attention. Memory T stem cells defined by CD95+ are long-lived and have the capacity for self-renewal and multidifferentiation. We also identified a novel memory T cell population, young memory T cells defined by CD73+CXCR3+. Regulation of such memory T stem cells will be useful for peptide vaccination and adoptive cell transfer.
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: b Department of Orthopaedic Surgery , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.|b Department of Orthopaedic Surgery , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Murata
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.|b Department of Orthopaedic Surgery , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Mizushima
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.|b Department of Orthopaedic Surgery , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shibayama
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: b Department of Orthopaedic Surgery , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: a Department of Pathology , Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012509:Sarcoma / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell
keywords: Osteosarcoma; immune checkpoint inhibitor; memory T stem cell; peptide vaccination; synovial sarcoma