Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities

Mol Cells. 2023 Oct 31;46(10):579-588. doi: 10.14348/molcells.2023.0079. Epub 2023 Sep 22.

Abstract

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

Keywords: bone cancer; immunotherapy; sarcomas; soft tissue sarcoma; tumor microenviorment.

Publication types

  • Review

MeSH terms

  • Cancer Vaccines* / therapeutic use
  • Humans
  • Immunotherapy
  • Male
  • Sarcoma* / drug therapy
  • Sarcoma* / pathology
  • Tumor Microenvironment

Substances

  • Cancer Vaccines

Grants and funding

ACKNOWLEDGMENTS This work was supported by grants from the National Research Foundation of Korea (NRF-2023R1A2C3003864 and RS-2023-00213119); Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (RS-2023-00217266); the Institute for Basic Science from the Ministry of Science, ICT, and Future Planning of Korea (IBS-R008-D1); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (HI21C1218); and Suh Kyungbae foundation (18010068).