Author(s): Noah Moffat, Clark Tolbert, Colin Wessman
Mentor(s): Matthew Bailey
Institution BYU
Pediatric cancers are fundamentally different from their adult counterparts. Specifically, pediatric cancers carry fewer mutations, interact with developing immune systems, and have active developmental microenvironments. The tumor microenvironment, which includes the surrounding stromal cells, immune cells, blood vessels, and extracellular matrix, plays a crucial role in cancer progression, metastasis, behavior, and response to treatment. To better understand the effects of the pediatric tumor microenvironment on tumor gene expression, spatial transcriptomic data from 5 studies (18 pediatric brain tumors and 25 adult brain tumors) was acquired and analyzed through a cancer hallmarks framework. The cancer hallmarks framework provides a comprehensive set of 13 biological capabilities acquired by cancer cells that enable tumor growth and metastasis. We compared the expression of cancer hallmarks between the microenvironment compartment and neoplastic compartment. We identify 4 cancer hallmarks (deregulating cellular energetics, senescent cells, resisting cell death, and evading growth suppressors) that are more active in the microenvironments of pediatric samples, but more active in the neoplastic compartments of adult samples. We also find that hallmark expression in the microenvironment highly correlates with epigenetic reprogramming in the neoplastic compartment. These findings underscore the critical role of the tumor microenvironment in driving the unique biology of pediatric cancers, and highlight the need for targeted therapies that address these microenvironmental influences.