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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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Similarly, the cumulative presence of variants in oxidative stress-related genes such as GSTM1, MPO, OGG1, TP53, and MMP1 was associated with a markedly increased risk of lung cancer in a Thai population, particularly among women, suggesting that inherited deficiencies in ROS-handling mechanisms may exacerbate the effects of environmental exposures like radon and passive smoking (82)

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