The causal impact of complement C3d receptor 2 on head and neck cancer microenvironment and its implications for immunotherapy response prediction.

This research dives into the intricate immune landscape of head and neck cancer (HNC), with a keen focus on the roles of specific immune cell subpopulations and their linked genes. We used tumour RNA-seq (in-house cohort: n = 192, TCGA-HNSC: n = 546) and Mendelian randomization to pinpoint key SNPs in immune cells that have a causal connection to HNC. Our discoveries unveil a spectrum of tumour immune phenotypes that either offer protection against or increase the risk of HNC. We underscore the therapeutic promise of Complement C3d Receptor 2 (CR2), a gene closely tied to immune cells, with its increased expression in tumour tissues linked to a more favourable prognosis. This is correlated with heightened immune pathway activity, stronger resistance to radiochemotherapy, and improved immunotherapy responses. Our research emphasises the pivotal role of CR2 in immune regulation and the significance of immune cells in tumour progression, highlighting the potential of CR2-targeted therapeutic interventions.