Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients
2023
Dan Yan
EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive <i>EGFR</i> mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced <i>EGFR</i>-mutant NSCLCs. Although immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs, ICI therapy exhibits limited activity in most <i>EGFR</i>-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in <i>EGFR</i>-mutant NSCLCs contributes to a non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8<sup>+</sup> T cell infiltration, a high number of regulatory CD4<sup>+</sup> T cells, and an increased number of inactivated infiltrated T cells. Additionally, <i>EGFR</i>-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. Promisingly, a small population of <i>EGFR</i>-mutant NSCLCs still durably respond to ICI therapy. The hope of ICI therapy from pre-clinical studies and clinical trials is reviewed in <i>EGFR</i>-mutant NSCLCs. The challenges of application ICI therapy in <i>EGFR</i>-mutant NSCLCs are also reviewed.
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