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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Immunotherapy in Sarcoma: Where Do Things Stand?

Cristiam Moreno Tellez1, Yan Leyfman2, Sandra P D'Angelo3

  • 1Department of Medicine, University of Colorado School of Medicine, 12801 E 17th Avenue, Mailstop 8117, Aurora, CO 80045, USA.

Surgical Oncology Clinics of North America
|June 17, 2022
PubMed

Early experiences with modern immunotherapy have been disappointing in trials of unselected sarcoma subtypes. However, remarkable efficacy has been observed with immune checkpoint inhibitors (ICIs) in a subset of patients, with the most promising outcomes to date in alveolar soft part sarcoma, cutaneous angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and dedifferentiated liposarcoma (dLPS). Adoptive cellular therapies targeting cancer testis antigens have shown promising activity, but only synovial sarcoma (SS) and myxoid/round cell liposarcomas reliably express these targets. The majority of sarcomas are immunologically "cold" with sparse immune infiltration, which may explain the poor response to immunotherapy. Current immunotherapy trials for sarcomas explore combination therapies with checkpoint inhibitors to overcome immune evasion and novel targets in adoptive cellular therapies. The role of tertiary lymphoid structures, PD-L1 expression, tumor mutational burden, microsatellite instability, and tumor lymphocytes as biomarkers for response are areas of active investigation. In this review, we highlight prior and ongoing clinical efforts to improve outcomes with immunotherapy and discuss the current state of understanding for biomarkers to select patients most likely to benefit from this approach.

Keywords:
Adoptive cellular therapyImmune checkpoint inhibitorsImmunotherapySoft tissue sarcomaTertiary lymphoid structureTumor microenvironment

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