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Dual Roles of hABCB1 in Drug Resistance and Immune Evasion: Implications for Lung Cancer Therapy

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Multidrug resistance mediated by ATP-binding cassette transporter B1 (ABCB1) remains a major obstacle in nonsmall cell lung cancer (NSCLC) therapy. While its role in drug efflux is well established, whether elevated ABCB1 expression is associated with broader immune-related phenotypes has not been completely elucidated. Here, we examined hABCB1-overexpressing and drug-adapted NSCLC models to assess coordinated changes in drug resistance and immune susceptibility. Increased ABCB1 expression was associated with enhanced efflux activity and reduced sensitivity to chemotherapeutic agents. Across engineered and drug-selected systems, ABCB1-high cells showed decreased susceptibility to NK-92-mediated cytotoxicity. Pharmacological inhibition of transporter activity partially increased effector-mediated killing, supporting ABCB1 activity as a contributing factor, while indicating that additional mechanisms may also be involved. Proteomic and cytokine profiling suggested coordinated alterations in inflammatory and interferon-related signaling pathways. In a human lung cancer tissue microarray, elevated hABCB1 expression was inversely associated with CD3 + T-cell infiltration. Together, these findings support an association between elevated ABCB1 expression and both drug-resistance features and immune-related phenotypes in NSCLC. Further genetic and in vivo studies are required to define mechanistic causality and clinical relevance.

Source: ACS Omega

DOI: 10.1021/acsomega.5c08960