**1. Introduction**

Lung cancer is the leading cause of cancer death worldwide [1]. Current clinical studies have shown that some types of molecularly targeted therapies are able to successfully treat a subset of patients with advanced non-small cell lung cancer (NSCLC). In addition, cancer immunotherapies, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint inhibitors, are being developed as promising alternative strategies for treating patients with advanced NSCLC. Of the current immune checkpoint inhibitors (ICIs), nivolumab, pembrolizumab, atezolizumab, and durvalumab have been approved in the United States, Japan, and other countries for the treatment of patients with NSCLC based on phase III clinical trials [2–6]. However, the majority of patients with NSCLC ultimately acquire resistance to ICI treatments. After acquiring resistance to several therapeutic regimens, ICI rechallenge is considered to be one of the therapeutic options for patients with recurrent NSCLC. Unfortunately, ICI rechallenge treatment has been clinically effective in only a small number of NSCLC patients. Therefore, it is warranted to identify predictive clinical markers for the effectiveness of ICI rechallenge. Previous retrospective studies regarding ICI rechallenge have analyzed only limited numbers of NSCLC patients [7,8]. Hence, little is currently known regarding the effectiveness and tolerability of ICI rechallenge after disease progression following initial ICI treatments. In an effort to identify the patients eligible for ICI rechallenge treatment, we retrospectively analyzed the relationship between the clinical profiles and the effect of ICI rechallenge in patients with NSCLC.
