Activating Immune Landscape within Solid Tumor Microenvironment in Pediatric and AYA Sarcoma

Despite ongoing success of immunotherapy approaches, including CAR T therapy and immune checkpoint blockade therapies, in many cancers, application of these successful strategies for cancers that affect childhood and the adolescents & young adults (AYA) age group have been largely disappointing. In particular, progress in the effective management of relapsed, recurrent or metastatic sarcoma, including Osteosarcoma (OS) and Rhabdomyosarcoma (RMS), have been stagnant. New therapeutic development and additional insights into understanding the immune-hostile sarcoma tumor microenvironment are desperately needed. We have recently demonstrated antitumor activities of a small molecular inhibitor targeting  TGF-beta signaling in preclinical OS models that has led to an ongoing Phase I/II clinical trial (NCT05588648). In addition, we have also interrogated molecular and cellular mechanisms driving immune-related abscopal effects in mouse models of RMS using cryoablation, a technique commonly used in clinical management of bulky solid tumors with inconsistent clinical outcome. This presentation will present these preclinical evidence and insights gained from such exploration and offer potential future clinical translational impact in the management of these devastating diseases.

Learning Objectives:

1. Discuss challenges associated with pediatric and young adult sarcoma management

2. Demonstrate potential impact of direct targeting of an immune suppressive factor in sarcoma therapy

3. Clarify relative contributions of innate sensor activation in sarcoma TME in response to cryotherapy