Emerging Trends in Immunotherapy for Adult Sarcomas

Abstract

Soft-tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that arise from the oncogenic transformation of mesenchymal tissue. There are over 100 distinct STS histological and molecular subtypes with unique clinical, therapeutic, and prognostic features with variable responses to therapy regimens. Given the quality-of-life concerns and limited efficacy with current regimens, including cytotoxic chemotherapy, there is a need for novel therapies and regimens to treat advanced STS. Although immune checkpoint inhibitors have demonstrated significant improvements in survival outcomes in other cancer types, there remains ambiguous data on the impact of immunotherapy in sarcoma. Biomarkers like PD-1/PD-L1 are not always predictive of outcomes. Therefore, researching emerging novel therapies, such as CAR-T and adoptive cell therapies, is critical to understanding STS biology, STS tumor immune microenvironment immunomodulatory strategies that improve immune response, and survival outcomes. We discuss the underlying biology of the STS tumor immune microenvironment, immunomodulatory strategies that augment pre-existing immune responses, and novel approaches to develop sarcoma-specific antigen-based therapies.

Serial neutrophils count as a stratifying tool for early follicular tonsilitis remission

“…The most common reason is a change in the concentration of the agent causing the problem or a change in the way the host and parasite interact. [32][33][34][35][36][37][38][39][40][41] Regarding EFT, it can indicate the initiation or occurrence of a particular immune response to the pathogens responsible for the condition. Three patients experienced complete resolution of EFT following a double-blind trial of oral flucloxacillin.…”

Immunotherapy Plus Radiotherapy for the Treatment of Sarcomas: Is There a Potential for Synergism?

“…106,107 This suggests that the population that most likely to benefit from immunoradiotherapy are those with subtypes of sarcomas that are sensitive to immunotherapy and/or radiotherapy, such as those with UPS or synovial sarcoma. Because UPS is a subtype of sarcoma that is sensitive to both radiotherapy and PD-1 inhibitor therapy; 11,12 Synovial sarcoma is a subtype of sarcoma that is sensitive to both radiotherapy and adaptive cellular therapy or cancer vaccine. 17,18,[108][109][110] The authors of these clinical case reports claim that radiotherapy has an abscopal effect on sarcomas.…”

“…9,10 At present, the widely used immunotherapies in clinical practice include programmed death receptor-1 (PD-1)/programmed death protein ligand-1 (PD-L1) inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors, and the new types of immunotherapy include adoptive cellular therapies and cancer vaccines. 11,12 PD-1/L1 and CTLA-4 inhibitors have promising efficacy (with a response rate of 10-28%) in the treatment of a few pathological subtypes of STS (undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, alveolar soft part sarcoma and angiosarcoma), and their efficacy in the treatment of other subtypes of STS are limited. 11,[13][14][15] Among approaches of adaptive cellular therapies, only engineered T-cell receptor (TCR) therapy has achieved remarkable efficacy in synovial sarcoma, with a response rate of over 50%.…”