VTCN1 emerges as a biomarker of immune tolerance in osimertinib-resistant lung cancer.

Abstract

Osimertinib is an effective strategy for nonsmall-cell lung cancer (NSCLC). However, the acquired resistance neutralizes the efficacy of osimertinib. Herein, we investigated the potential biomarkers of osimertinib-resistant lung cancer. GSE200894 was used to analyze the differentially expressed genes in osimertinib-resistant lung cancer. Sixty-two paired surgical specimens were collected from NSCLC patients with stage I-IV. Gene expression was detected using reverse transcription (RT)-qPCR, western blot, and immunohistochemistry. V-set domain containing T cell activation inhibitor 1 (VTCN1) was overexpressed in osimertinib-resistant lung cancer. High levels of VTCN1 predicted advanced stages and distant metastasis. Moreover, VTCN1 expression was negatively correlated with the purity of CD8+ T cells in lung cancer patients. VTCN1 inhibits the infiltration of effector-memory CD8+ T cells. In addition, overexpressed VTCN1 predicted the exhaustion of CD8+ T cells. VTCN1 inhibits the tumor-killing ability of CD8+ T cells. In summary, VTCN1 is overexpressed in osimertinib-resistant lung cancer patients. High levels of VTCN1 confer to inhibition of CD8+ T cell immunity and immune tolerance in osimertinib-resistant lung cancer patients.