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5.3 Remodeling of the immune microenvironment In the immune combination strategy to address gemcitabine resistance, CD40 agonist activation of antigen presentation and oncolytic virus-induced “viral mimicry” to enhance immunogenic cell death (ICD) are two key directions, which can enhance the efficacy of chemotherapy and reverse resistance by reshaping the immune microenvironment: CD40 agonists (such as Selicrelumab) promote tumor antigen presentation and T cell activation by activating CD40 receptors on the surface of dendritic cells (Vonderheide, 2020), and form an “antigen release-presentation-response” closed loop when combined with gemcitabine

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Sci Rep 15 , 16707 (2025)