Immunotherapy strategy of EGFR mutant lung cancer

Abstract

EGFR-mutant lung cancer is an important molecular subtype in Asia considering that almost 40%-50% of patients with lung adenocarcinoma in Asian carry the active EGFR mutaiton. People have greatly anticipated the efficacy of PD-1/PD-L1 monoclonal antibody in lung cancer treatment but anti-PD-1/PD-L1 treatment failed to positively affect these patients. The NCCN guidelines do not recommend immunotherapy to patients with NSCLC carrying EGFR mutation at present. However, the reason why EGFR-mutant lung cancer patients show poor response to anti-PD-1/PD-L1 treatment is still unknown. Immune suppression and tolerance are the main characteristics of tumor. The PD-1/PD-L1 co-inhibitory molecule is probably not the main escape route of this tumor type. The main characteristic of EGFR-mutant lung cancer is the activation of the EGFR signaling pathway. EGFR activation is likely responsible for the uninflamed tumor microenvironment of this type tumor and particiaptes in immunosuppression and immune escape. Accumulating evidence proved that activation of EGFR signaling pathway is essential to the generation of Treg and tolerogenic DCs. In this review, we summarize the efficacy of PD-1/PD-L1 monoclonal antibiodies in patients with EGFR-mutant lung cancer patients; provide evidence to analyze the potential reason why these patients cannot benefit from anti-PD-1/PD-L1 treatment, and explore the strategy that shoud be adopted in the future.

Keywords: EGFR mutation; immunotherapy; lung cancer.

Figure 1

EGFR signaling and generation of Treg and tol-DC. EGFR signaling pathway activation can promote generation of Treg cells and tol-DC and maintain the suppression function of Treg cells and tol-DC.