First-line Immunotherapy and Clinically Meaningful Survival Benefits for the Oldest Adults With Lung Cancer

Charlot, Marjory; Gray, Jhanelle E.

doi:10.1001/jamaoncol.2022.6867

Cited by 1 publication

(1 citation statement)

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“…54 Patients achieving pathological remission exhibit improved long-term survival outcomes. 55 However, targeted therapies, especially EGFR-TKIs, show only a lower rate of pathological remission. 56 57 Prolonged treatment with TKIs induces significant changes in the TME, including increases in the expression of immune inhibitory factors, such as PD-L1, suppression of the type I IFN signaling pathway, reduced immune cell activity, and the initiation of immune escape mechanisms.…”

Section: Open Accessmentioning

confidence: 99%

Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect

Lu,

Gao,

et al. 2024

J Immunother Cancer

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BackgroundThe dynamic interplay between tyrosine kinase inhibitors (TKIs) and the tumor immune microenvironment (TME) plays a crucial role in the therapeutic trajectory of non-small cell lung cancer (NSCLC). Understanding the functional dynamics and resistance mechanisms of TKIs is essential for advancing the treatment of NSCLC.MethodsThis study assessed the effects of short-term and long-term TKI treatments on the TME in NSCLC, particularly targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. We analyzed changes in immune cell composition, cytokine profiles, and key proteins involved in immune evasion, such as laminin subunit γ−2 (LAMC2). We also explored the use of aspirin as an adjunct therapy to modulate the TME and counteract TKI resistance.ResultsShort-term TKI treatment enhanced T cell-mediated tumor clearance, reduced immunosuppressive M2 macrophage infiltration, and downregulated LAMC2 expression. Conversely, long-term TKI treatment fostered an immunosuppressive TME, contributing to drug resistance and promoting immune escape. Differential responses were observed among various oncogenic mutations, with ALK-targeted therapies eliciting a stronger antitumor immune response compared with EGFR-targeted therapies. Notably, we found that aspirin has potential in overcoming TKI resistance by modulating the TME and enhancing T cell-mediated tumor clearance.ConclusionsThese findings offer new insights into the dynamics of TKI-induced changes in the TME, improving our understanding of NSCLC challenges. The study underscores the critical role of the TME in TKI resistance and suggests that adjunct therapies, like aspirin, may provide new strategies to enhance TKI efficacy and overcome resistance.

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Section: Open Accessmentioning

confidence: 99%