fig5

Figure 5. Summary of intrinsic and extrinsic mechanisms of resistance in SCLC and potential therapeutics to overcome resistance. Mechanism-directed strategies to overcome immunotherapy resistance and biomarker-driven therapies address the inherent heterogeneity in SCLC. The extrinsic mechanisms of resistance via interactions with the TME are comprised of a complex interplay of immune cells, vasculature, immune checkpoints, and microbiome. Therapies that may target aspects of the TME include cellular therapies, cytokine therapies, anti-angiogenesis agents, and immune checkpoint inhibitors. Intrinsic mechanisms of resistance, which include decreased tumor immunogenicity, altered antigen presentation machinery, immune checkpoints, and epigenetic modifications, may also be avenues for targeted therapies. SCLC: Small cell lung cancer; TME: Tumor microenvironment; CAR-T: Chimeric antigen receptor T-cell therapy; PARP: Poly-ADP ribose polymerase; STING: Stimulator of interferon genes.