Emma Wagner

All Publications

• Development of functional spatial mapping of the tumour immune microenvironment (FuncO:TiME) in advanced melanomas. BJC reports Wagner, E., Legg, S., Applebee, C. J., Kirane, A. R., Padget, J., Larijani, B. 2026; 4 (1)

  Abstract

  Current spatial proteomic approaches quantify immune checkpoint expression but do not directly measure functional receptor-ligand (PD-1/PD-L1) interactions within the tumour-immune microenvironment (TiME). Therapeutic antibodies disrupt receptor-ligand interactions and do not target protein abundance; therefore, methods capable of resolving functional checkpoint interactions may provide biologically distinct insight beyond expression-based assays.We developed FuncO:TiME by integrating functional oncology mapping (FuncOmap), histopathology and multiplex spatial immune profiling to map PD-1/PD-L1 interaction states within clinically annotated melanoma tissues collected before and after neoadjuvant immune checkpoint blockade (ICB).FuncOmap quantified millions of per-pixel PD-1/PD-L1 interactions and revealed marked spatial heterogeneity in checkpoint interactions that were not reflected by PD-1 or PD-L1 expression alone. Post-treatment tissues exhibited increased PD-1/PD-L1 interaction states despite no corresponding increase in expression, highlighting the divergence between functional checkpoint interactions and expression-based measurements. Integrating with spatial immune profiling further demonstrated the feasibility of contextualising regional differences in interaction states within distinct immune populations and patterns of PD-1/PD-L1 expression in melanoma TiMEs.We establish the feasibility of FuncO:TiME spatially resolved mapping of functional checkpoint interactions in human melanoma tissues. Our findings demonstrate that receptor-ligand interactions diverge from checkpoint protein expression patterns and support further development of integrated approaches that contextualise functional checkpoint interactions within cellular features of the TiME. Such approaches may enable deeper investigation of checkpoint biology and inform the future development of functionally informed biomarkers for cancer immunotherapy.

  View details for DOI 10.1038/s44276-026-00250-w

  View details for PubMedID 42816549

  View details for PubMedCentralID 10961546

• AXL tyrosine kinase inhibition restores anti-PD-1 efficacy in melanoma through tumor-associated macrophage-dependent mechanisms Kirane, A., Lee, D., Sharma, S., Safrygina, E., Applebee, C., Serasanambati, M., Wagner, E., Delitto, D., Padget, J., Maverakis, E., Larijani, B. OXFORD UNIV PRESS. 2026

  View details for DOI 10.1093/jimmun/vkag141.277

  View details for Web of Science ID 001834280300001

• Spatial characterization and predictive implications of the tumor immune micro-environment in stage III melanoma under neoadjuvant immunotherapy. Zhang, Y., Wagner, E., Hurtado, A., Chadokiya, J., Funchain, P., Kirane, A. R., Betof, A. LIPPINCOTT WILLIAMS & WILKINS. 2026: e21534

  View details for DOI 10.1200/JCO.2026.44.16_suppl.e21534

  View details for Web of Science ID 001780645000025

• Label-free spatial profiling of the melanoma tumor microenvironment using metasurface-enhanced Raman spectroscopy. Chang, K., Serasanambati, M., Naba, F., Bordoloi, P., Georgiadis, A., Wagner, E., Delgado, H., Chen, C., Dolia, V., Ogunlade, B., Dado, R., Stiber, A., Hu, J., Kirane, A. R., Dionne, J. AMER ASSOC CANCER RESEARCH. 2026

  View details for DOI 10.1158/1538-7445.AM2026-697

  View details for Web of Science ID 001734581500019

• Predictive Biomarkers for Immune Checkpoint Inhibitor Therapy in Advanced Melanomas. Surgical oncology clinics of North America Wagner, E., Larijani, B., Kirane, A. R. 2025; 34 (3): 437-451

  Abstract

  Biomarkers capable of predicting adverse melanoma patient responses to immune checkpoint inhibitor (ICI) therapies are an unmet need. Clinical biomarkers are largely prognostic and current response guidelines do not reflect the complex tumor-immune cell interaction dynamics attributed to ICI therapies. Validation of enhanced predictive biomarkers is dependent upon adoption of novel spatial imaging platforms capable of quantifying immune checkpoint receptor-ligand interactions within the tumor microenvironment. Assessments of these interactions at multiple points during neoadjuvant ICI regimens would inform biomarker selection based on changes in receptor-ligand interactions that best correlate with patient survival.

  View details for DOI 10.1016/j.soc.2025.01.006

  View details for PubMedID 40413009