Advanced

the most common cancer men with of 1 in this of in treating these patients with immunomodulatory of patients remain refractory to therapeutic intervention. EphB4 and Eph-rinB2 are induced in the tumor vasculature and modulate immune response within the tumor microenvironment. Inter-vention blocking Ephrin and PD-1/PD-L1 pathway has shown promising data in preclinical models. These data form the basis of clinical investigation of combined therapy in bladder cancer and other tumor types. and secondary tumor sites, resulting in tumor mass reduction in post-treatment observations. DSP between matched samples discovered interesting differences in T-cell populations between both protein and mRNA expression. We observed evidence of tumor-debulking by decreased expression of epithelial markers such as Pan-cytokeratin and S100B within tumor ROIs, and increased infiltration within these ROIs measured by immune cell markers such as CD3 and CD163. Additionally, we observed increased GZMA expression post-treatment in peri-vascular regions suggestive of higher ongoing response by cells entering the tumor microenvironment. Additional analysis of localized RNA expression provided further support for activa-tion of inflammatory cascades in post-treatment samples. Conclusions These discoveries provide insights into the mecha-nism of action of EphB4 combination therapy in bladder cancer, providing support for a role of EphB4 acting as an adjuvant for PD1 therapy. Our results highlight the ability of EphB4 to activate the immune system both in preclinical models and in key structures within the tumor microenvironment during combination therapy.