Immunotherapy for small cell lung cancer: mechanisms of resistance

ABSTRACTIntroduction: Small cell lung cancer (SCLC) is a highly malignant disease with a dismal prognosis that is currently being tested for theclinical activity of checkpoint inhibitors. SCLC is associated with smoking and exhibits a high mutational burden. However, low expression of PD-L1 and MHC antigens, as well low levels of immune cell infiltration and rapid tumor progress seems to limit the efficacy of anticancer immunity. Nevertheless, long-term survival was reported from studies using anti-PD-1/PD-L1 and CTLA-4 agents.Areas covered: Data of clinical trials of checkpoint inhibitors in SCLC show lower success rates compared to NSCLC. The mechanisms of resistance to immunotherapy are discussed for their relevance to SCLC patients.Expert opinion: Although some factors, such as a high mutation rate, favor immunotherapy for SCLC patients, downregulation of MHC class I, low expression of PD-L1, poor tumor infiltration by effector T cells, presence of myeloid-derived suppressor cells as well as regulator...