TIME to Target Sarcomas: Lessons from the Tumor Immune Microenvironment

The tumor immune microenvironment (TIME) has emerged as a crucial regulator of antitumor immune responses with important therapeutic, prognostic, and predictive implications. Despite the success of immunotherapies in select solid tumors, notably melanoma and non-small cell lung cancer, their impact in soft-tissue sarcomas (STSs) is limited, often attributed to an immune-cold TIME passively driven by low neoantigen burden. Herein, we review the current understanding of the STS TIME, its variability across STS subtypes, and its implications for STS immunotherapy. We propose that the prevailing view of STSs as passively immune-cold is incomplete and that active tumor-driven immune suppression is likely underappreciated. Distinguishing active from passive immune escape and understanding its mechanistic underpinnings will be important to rationally design effective TIME-targeted therapies in STSs and to serve as a paradigm for therapeutic interventions in other immune-cold tumors.