Sarcomas comprise a collection of highly heterogeneous
malignancies that can be grossly grouped in the categories of
sarcomas with simple or complex genomes. Since the outcome for most
sarcoma patients has barely improved in the last decades, there is an urgent need for improved
therapies.
Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in
cancer therapy as it produced significant and durable treatment responses in several
cancer types. Currently, only a small fraction of
sarcoma patients benefit from
immunotherapy, supposedly due to a general lack of somatically mutated
antigens (neoantigens) and spontaneous T cell immunity in most
cancers. However, genomic events resulting from
chromosomal instability are frequent in
sarcomas with complex genomes and could drive immunity in those
tumors. Improving our understanding of the mechanisms that shape the immune landscape of
sarcomas will be crucial to overcoming the current challenges of
sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in
sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of
immunotherapy, and which could provide new avenues for the treatment of
sarcomas.