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.
Highlights
Soft tissue sarcomas (STS) are a group of over 100 rare cancers of definite or suspected mesenchymal origin/differentiation, typically classified by morphological and immunophenotypic characteristics
This study suggests a combination of doxorubicin and maternal embryonic leucine zipper kinase (MELK) inhibitor treatment could act synergistically by preventing M2 tumour-associated macrophages (TAMs) polarisation and increasing doxorubicin sensitivity in uterine LMS [110], MELK inhibition has yet to be assessed in STS in a clinical setting
The progress of IO in sarcoma has been lacking when compared to other cancer types, such as melanoma and NSCLC, primarily due to the rare and heterogeneous nature of this group of diseases
Summary
Soft tissue sarcomas (STS) are a group of over 100 rare cancers of definite or suspected mesenchymal origin/differentiation, typically classified by morphological and immunophenotypic characteristics. Such a classification, only partly describes the wide range of clinical behaviour that is exhibited both within and between the histologically defined subtypes. Other STS subtypes are known to be associated with a high degree of chromosomal copy number abnormalities Despite this improved knowledge, progress in developing effective new systemic therapies in STS has been disappointingly slow. The reported sensitivity of certain rare, genomically bland STS subtypes to immune checkpoint inhibitors (CPIs) [8] gives rise to questions that challenge the prevailing theories as to what determines a cancer’s response to such therapies. We discuss potential avenues to broadening the effectiveness of IO within STS
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