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Small-cell lung cancer (SCLC) is a clinically aggressive cancer, and accounts for 15% of all types of lung cancer. SCLC is characterized by its rapid growth, early dissemination, and easy acquisition of multidrug resistance to chemotherapy. While most of the patients with SCLC are eligible to systemic chemotherapy owing to the presence of distant metastasis at the time of diagnosis, the median survival with the standard chemotherapy is less than 12 months. Numerous clinical trials, including molecular targeted therapy, have been conducted in hopes of developing a novel therapeutic strategy in SCLC, but eventuated disappointed results. Consequently, the standard chemotherapeutic regimen has not changed for three decades. Moreover, clinically beneficial therapeutic strategies for patients with relapsed-SCLC are extremely limited. Thus, effective treatment of SCLC has been leveling off in spite of the recent dramatic progress in the treatment of non-SCLC. Genomic analysis revealed that definitively targetable molecules with oncogenic driver activity were rarely detected

in SCLC. Therefore, immunotherapy rather than molecular targeted therapy is considered to be promising in the improvement of prognosis in patients with SCLC. Immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab have been approved for the treatment of the patients with non-SCLC, and have dramatically improved their prognosis. These ICIs exert antitumor effect via activating adaptive immunity. Some clinical trials have demonstrated promising effects of ICIs in the treatment of relapsed-SCLC. We have reported that trastuzumab, a humanized anti-human epidermal growth factor receptor 2 antibody, could exert remarkable antitumor effects against SCLC mainly through antibody-dependent cell-mediated cytotoxicity (ADCC) in preclinical models and clinical settings. ADCC is commonly recognized as one of the best ways to activate innate immunity. It is essential to clarify how to maximize the benefit of the immunotherapy in order to improve the prognosis of SCLC.