Small cell lung carcinoma (SCLC) is a type of lung cancer that accounts for about 15% of all lung cancer cases. Although SCLC patients initially respond to chemotherapy and immune checkpoint blockade (ICB), however, resistance invariably emerges. Currently, there are no predictive biomarkers of response, and patients with SCLC continue to have a poor prognosis with limited treatment options. Recent multiparametric profiling of SCLC cell lines and patient samples has revealed significant inter-tumoral and intra-tumoral heterogeneity. Non-neuroendocrine (Non-NE) SCLC exhibits increased innate immune signaling and robust upregulation of antigen presentation on MHC-I, whereas neuroendocrine (NE) SCLC subpopulations downregulate MHC-I. Based on this, MHC-I low SCLC was predicted to be vulnerable to NK cell-mediated control.