Correlation between T cell immunity and the duration of EGFR-TKI resistance acquisition in patients harboring EGFR mutations

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) control lung cancer in patients with EGFR mutations, but resistance develops over time. Patients with high levels of genetic mutations rapidly acquire EGFR-TKI resistance. T cell immunity recognizes gene mutation products as neoantigens that effectively suppress mutation levels by eliminating clones with more mutations; this process is known as cancer immune editing. Therefore, EGFR-TKI-resistant clones may be less likely to form in cases with active antitumor T cell immune responses. However, the relationship between EGFR-TKI resistance and antitumor T cell response in patients with EGFR mutation remains unclear. To determine the relationship between the duration of EGFR-TKI resistance acquisition and antitumor T cell immunity, and the effect of EGFR-TKIs on T cell immunity. This prospective observational study enrolled 43 patients who received osimertinib. Blood samples were collected prior to and following 4 weeks of EGFR-TKI administration. The median PFS and OS for the 37 patients were 24.8 and 32.9 months, respectively. Patients with higher CXCR3 + CCR4 − CCR6 + CD4 + T cell levels exhibited significantly enhanced PFS ( p = 0.002) and OS ( p = 0.0006). Other T cell subsets (Th1, Th2, Th17, and CD8 + ) exhibited no significant correlation with PFS. The percentage of CXCR3 + CCR4 − CCR6 + CD4 + T cells was significantly reduced with tumor volume reduction ( p < 0.0001). T cell immunity affects the time required to acquire resistance after EGFR-TKI treatment. Pretreatment CXCR3 + CCR4 − CCR6 + CD4 + T cell cluster was significantly associated with PFS after osimertinib treatment, likely predicting osimertinib efficacy. Antitumor T cell immunity may be crucial for preventing the acquisition of EGFR-TKI resistance.

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