Abstract Background: Nasopharyngeal carcinoma (NPC) is an aggressive cancer of the head and neck that is strongly associated with the Epstein-Barr virus (EBV). Coupled with its dense immune populations and high PD-L1 expression, immune checkpoint blockade (ICB) has emerged as a promising treatment for NPC. Unfortunately, ICB efficacy in NPC remains unsatisfactory and highly variable, often undermined by evasive mechanisms such as disrupted vasculature which hinders T cell infiltration for tumour killing. We hypothesize that anti-angiogenic therapy can boost anti-tumour immunity and in turn synergise ICB efficacy in NPC. Here, we sought to elucidate biomarkers and immune signatures that associate with response towards this combinatorial treatment. Methods: Here, we profiled 96 pre-treatment and on-treatment plasma samples from 17 recurrent and metastatic (R/M) NPC patients receiving pembrolizumab with and without prior bevacizumab priming (NCT03813394), using targeted proteomics (Olink® HT Explore Panel). We utilised differential expression analysis to identify differentially expressed proteins and pathway enrichment analyses were performed with ShinyGO (v0. 77) and STRING (v12. 0). Results: We stratified patients’ proteome based on their long-term survival into two groups, and observed a drastic, early treatment-induced proteomic rewiring that is unique to good responders. This includes the upregulation of 108 immune factors mostly involved in immune activation. Pathway enrichment and protein-protein network analyses revealed increased lymphocyte-stimulatory (CCL5, CCL20) and anti-viral inflammatory pathways (IL-1β, IFN-λ1), positing their associated proteins as potential biomarkers of response. Conclusion: Our study revealed early serum proteomic changes relating to immune activation in R/M NPC patients who responded well to anti-VEGF/anti-PD1 combinatorial treatment. Given the anatomical inaccessibility of NPC, discovery of early-response, blood-based biomarkers can greatly improve patient prognosis and facilitate the stratification of likely responders to improve immunotherapy outcomes. Biomarkers identified will be subsequently validated in orthogonal protein assays, parallel multi-omics analyses and further explored in in vitro models. Citation Format: Shiqing Grace Goh, Tuan Zea Tan, Yaw Chyn Lim, Li Ren Kong, Boon Cher Goh. Elucidating Early Predictive Biomarkers for Immune Checkpoint Blockade (ICB) /Anti-angiogenic Combination Therapy in Advanced Nasopharyngeal Cancer (NPC) abstract. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85 (15Suppl): Abstract nr P73.
Goh et al. (Fri,) studied this question.