The future of immunotherapy for sarcoma

Expert Opin Biol Ther. 2016 Aug;16(8):1049-57. doi: 10.1080/14712598.2016.1188075. Epub 2016 May 27.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Osteosarcoma; immune checkpoint inhibitor; memory T stem cell; peptide vaccination; synovial sarcoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Humans
  • Immunotherapy* / methods
  • Immunotherapy, Adoptive / methods
  • Receptors, Antigen, T-Cell / metabolism
  • Sarcoma / immunology
  • Sarcoma / therapy*
  • T-Lymphocytes / immunology

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell