Single-cell spatial characterization of microenvironmental impacts on clinical discrepancies between adult and pediatric nasopharyngeal carcinoma patients

FARE Award Winner

Authors

• JY Kang
• Z Liu
• M Sun
• CJ Thiele

Abstract

Background
Nasopharyngeal carcinoma (NPC) is an EBV-related and highly inflamed malignancy of strategic importance in Asia and Africa. Only 0.1-1% of NPC incidences are diagnosed in children which exhibits superior prognosis and immunotherapy outcomes. Microenvironmental characteristics might contribute to such discrepancies between adult/pediatric NPC. Thus, we apply scRNA-seq and Visium spatial RNA-seq to pediatric NPC with paired blood, and incorporate our data with multi-central NPC cohorts. We report low lipid metabolism, weak tumor-T cell interactions, and enriched T memory stem cells (Tscm) collectively result in long-lasting immunity in pediatric NPC and as therapeutic vulnerabilities.

Method and results
We established a systematic NPC scRNA-seq and spatial-seq cohort containing 503,021 cells from 69 samples, and 15,222 spatial spots from 11 samples. We developed a personalized computational framework to characterize spatial co-localization and enriched signaling. We unveiled that fatty acid (FA)/cholesterol metabolism was elevated in adult NPC, and such metabolic aberrance was validated by lipid staining and blood tests. Strong co-localizations and interactions between NPC cells and Tregs/exhausted T cells were found in adult NPC. We identified novel Tscm populations in pediatric NPC, with resilience to immunosuppressive cues, and had an impact on long-term immunity and immunotherapeutic outcomes.

Conclusion
We demonstrate that higher immunosuppression and exhaustion caused by lipid metabolism and tumor-intrinsic interactions, and a lower Tscm pool, are the vital drivers of clinical discrepancies in adult/pediatric NPC patients. Pre-treatment screening of Tscm abundance in NPC patients might help stratify immunotherapy responders, and targeting metabolic and interacting vulnerabilities might benefit NPC patients.

Scientific Focus Area: Cancer Biology

This page was last updated on Monday, September 25, 2023