Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

Abstract Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but subset of SCLC has been termed “variant” due to the loss NE characteristics. In this study, we computed scores for patient-derived lines and xenografts, well human tumors. We aligned properties with transcription factor-defined molecular subtypes. Then investigated different immune phenotypes associated high low scores. found repression response genes shared feature between classic pulmonary cells healthy lung. With fate, variant tumors regain cell-autonomous gene expression exhibit higher tumor-immune interactions. Pan-cancer analysis revealed lineage-specific phenotype in other cancers. Additionally, observed MHC I re-expression upon development chemoresistance. These findings may help guide design treatment regimens SCLC.