UNCOVERING POTENTIAL TARGETS FOR PEDIATRIC CANCER IMMUNOTHERAPY: TRANSCRIPTOMIC PROFILING OF THE NEUROBLASTOMA TUMOR MICROENVIRONMENT

Abstract

Pediatric cancer patients have limited adoption of immunotherapy, despite their proven success in adult cancers. This study investigates neuroblastoma, with a focus on stage 4 and stage 4S, to examine differences in the immune infiltration and tumor-intrinsic features that influence disease progression and spontaneous regression. Bulk RNA sequencing and bioinformatics analyses were employed to assess immune cell infiltration, immune-suppressive cells, oncogenic pathways, and potential therapeutic targets. The results reveal that stage 4 tumors exhibit significant immune exhaustion of CD4+T cells and CD8+T cells, characterized by an immunosuppressive microenvironment. In contrast, stage 4S tumors display a functional immune response, with active CD8+ and CD4+ T cells associated with favorable outcomes. Additionally, oncogenic pathways linked to tumor aggressiveness and metastasis are enriched in stage 4 but downregulated in stage 4S. Notably, PLCL1, a candidate tumor suppressor involved in the phospholipase pathway, is significantly upregulated in stage 4S tumors, suggesting a potential role in tumor regression. This research highlights the significance of immune contexture in neuroblastoma and emphasize the need to restore immune functionality in high-risk patients. By utilizing insights from the spontaneous regression seen in stage 4S, these findings aid in the development of targeted immunotherapies for high-risk neuroblastoma.

Date of Award	2025
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences