Identifying Novel Targets for Enhancing Anti-PD1 Immunotherapy in Melanoma

Abstract

Checkpoint inhibitors targeting PD-1/PD-L1 have become prominent treatments for advanced melanoma. However, these inhibitors are effective in less than half of patients, highlighting the need for new pathways and strategies to improve response rates. Analysis of RNA sequencing data from melanoma patients receiving anti-PD1/PD-L1 therapy revealed an enrichment of FGFR signaling in nonresponders, which was associated with a poorer prognosis. Additionally, it was found that FGFR signaling is negatively correlated with B cell signaling in melanoma tumors. Conversely, B cell receptor signaling is enriched in responders' tumors and associated with a better prognosis. This suggests that inhibiting FGFR or increasing the activation of B cells may be novel therapeutic targets for melanoma patients and aid in checkpoint inhibitor therapy. Further validation is necessary to assess the impacts on anti-PD1/PD-L1 therapy response. Overall, characterizing distinguishable pathways between responders and nonresponders may lead to more personalized immunotherapy selections and improved clinical outcomes for advanced melanoma.