What type of study is this?

This is a Differential expression analysis study (also classified as: Targeted proteomics, Pathway enrichment analysis).

September 10, 2025

Abstract P73: Elucidating Early Predictive Biomarkers for Immune Checkpoint Blockade (ICB)/Anti-angiogenic Combination Therapy in Advanced Nasopharyngeal Cancer (NPC)

Key Points

Early serum proteomic changes indicate immune activation in patients responding to treatment for nasopharyngeal cancer.
Patients with good responses exhibited significant upregulation of immune factors—108 proteins involved in activating lymphocytes.
Differential expression analyses utilized targeted proteomics to identify protein patterns and pathways associated with treatment response.
Blood-based biomarkers can improve prognostic outcomes and help select patients likely to benefit from immunotherapy in nasopharyngeal cancer.

Abstract

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.

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