Current Status and Future Directions of Immunotherapies in Soft Tissue Sarcomas

Abstract

Immunotherapy in soft tissue sarcoma (STS) has experienced a surge of interest in the past decade, contributing to an expanding number of therapeutic options for this extremely heterogenous group of rare malignancies. Immune checkpoint inhibitors (CPIs) targeting the PD-1 and CTLA-4 axes have demonstrated promising responses in a select number of STS subtypes, including rarer subtypes, such as alveolar soft part sarcoma, SWI/SNF-deficient sarcomas, clear cell sarcoma, and angiosarcoma. Multiple pan-subtype sarcoma trials have facilitated the study of possible predictive biomarkers of the CPI response. It has also become apparent that certain therapies, when combined with CPIs, can enhance response rates, although the specific mechanisms of this possible synergy remain unconfirmed in STS. In addition to CPIs, several other immune targeting agents, including anti-tumour-associated macrophage and antigen-directed therapies, are now under assessment in STS with promising efficacy in some subtypes. In this article, we review the state of the art in immunotherapy in STS, highlighting the pre-clinical and clinical data available for this promising therapeutic strategy.

Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Standard of Care and Treatment Recommendations from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

“… 79 , 80 Promising findings regarding immune checkpoint inhibitors would also suggest a role for immunotherapy (PD1/PDL1 inhibitors) administered within clinical trials (if available) or on compassionate grounds. 81–84 …”

“…79,80 Promising findings regarding immune checkpoint inhibitors would also suggest a role for immunotherapy (PD1/PDL1 inhibitors) administered within clinical trials (if available) or on compassionate grounds. [81][82][83][84] Clear Cell Sarcoma CCS of tendons and aponeuroses is extremely rare in childhood and little information is available on its clinical behaviour in pediatric age. 35 It is generally described as a very aggressive tumor with a very limited responsiveness to standard chemotherapy.…”

Immunotherapy for Soft Tissue Sarcomas: Anti-PD1/PDL1 and Beyond

“…Nevertheless, a subset of patients showed remarkable and durable responses, after the failure of many traditional systemic treatments. Furthermore, recent research has restored hope in the possibility of sarcomas being treatable by immunotherapy [ 76 ]. One of the major challenges is to define the best candidates for these treatments by a better knowledge of each tumor’s immune component’s microenvironment and by the use of reliable biomarkers and response predictors, in order to optimize personalized medicine plans.…”

PD-1/L1 inhibitor plus chemotherapy in the treatment of sarcomas

“…Trabectedin selectively reduces monocytes and TAMs in treated tumors and can increase the presence and functional activity of T lymphocytes. In fibrosarcoma models with poor response to PD-1 immunotherapy, treatment with Trabectedin prior to anti-PD-1 can improve antitumor efficacy ( 77 , 78 ). In addition, an earlier study showed that the chemotherapy drug decitabine facilitates immune recognition of sarcoma cells by upregulating cancer/testis antigens, MHC molecules, and intracellular cell adhesion molecule-1 ( 79 ).…”