The Role of Immunotherapy in the Management of Soft Tissue Sarcomas: Current Landscape and Future Outlook
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Soft tissue sarcomas (STS) are a subset of sarcoma, a rare group of heterogeneous malignancies of mesenchymal origin. Current standard of care involves surgical resection with systemic chemotherapy used to treat high-risk localized and metastatic disease. Though classically thought to be immunologically quiet tumors, STS interact with the immune system, undergoing immunoediting that alters tumor immunogenicity and the tumor microenvironment. Recent advances with immune checkpoint inhibition have led to clinical trials exploring the efficacy of immunotherapy in treating STS. Results from these trials point to histologic subtype–specific clinical activity of immune checkpoint blockade. In addition, combinatorial strategies adding immune checkpoint inhibition to local or systemic therapies for STS have further increased their efficacy. Targeted immunotherapies using engineered T-cell receptor–based approaches also show increasing promise as treatment options for some patients with STS. Adoptive transfer of autologous T cells targeting NY-ESO-1 and MAGE-A4 have high response rates in sarcomas expressing these antigens, although recurrence is often seen in responding patients. Future work must focus on identifying primary and acquired mechanisms of resistance to these therapies, and extend T-cell receptor discovery to other tumor-associated antigens.
Submitted January 28, 2022; final revision received April 29, 2020; accepted for publication May 2, 2022.
Disclosures: Dr. D’Angelo has disclosed receiving grant/research support from Amgen Inc., Bristol-Myers Squibb Company, Deciphera Pharmaceuticals, EMD Serono Inc., Incyte Corporation, Merck & Co., Inc., and Nektar Therapeutics; serving as a consultant and on an advisory board for Adaptimmune Therapeutics PLC, Amgen Inc., EMD Serono Inc., GlaxoSmithKline plc, Immune Design Corp., Immunocore, Incyte Corporation, Merck & Co., Inc., Nektar Therapeutics, Pfizer Inc., Rain Therapeutics, and Servier Laboratories; serving on a data safety monitoring board for Adaptimmune Therapeutics PLC, GlaxoSmithKline plc, Merck & Co., Inc., and Nektar Therapeutics; and receiving travel, accommodation, and expense funding from Adaptimmune Therapeutics PLC, EMD Serono Inc., and Nektar Therapeutics. Dr. Banks has disclosed that not receiving any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: This work was supported in part by funding from the National Cancer Institute of the National Health Institutes under award number P50 CA217694.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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