SCLC molecular subtypes and tumor microenvironment (TME). This figure shows SCLC genetic alterations with a universal mutation of RB1 and TP53, along with mutations on MYC family and NOTCH that could guide a plasticity between neuroendocrine and non-neuroendocrine subtypes. Molecular classification based on four transcriptional factors is also shown: SCLC-A (ASCL1), SCLC-N (NEUROD1), SCLC-P (POU2F3), and SCLC-Y (YAP1). Finally, an immunosuppressive TME is represented, consisting of a low expression of PDL1, LAG3, and TIM3, MHC class I and II, APCs, TILs, low ratio lymphocyte T effector to regulator, and upregulation of CD47. However, SCLC-Y subtype is characterized by an immune inflamed TME with higher expression of PDL1, MHC molecules, immune cell infiltration, and INF-y signaling. PD-L1: programmed cell death ligand 1. TIM-3: T-cell immunoglobulin domain and mucin domain 3. LAG-3: lymphocyte activation gene 3. APCs: antigen presentation cell. TILs: tumor-infiltrating lymphocytes. MHC: major histocompatibility complex. LT eff: lymphocyte T effector. LT reg: lymphocyte T regulator. NE: neuroendocrine. NON NE: non-neuroendocrine.