AbstractSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.
Author Contributions:Anne Bakke: Conceptualization, Methodology, Writing – original draft preparation, Writing – review & editing; Alexander Rebl: Conceptualization, Methodology; Petter Frost: Writing – review & editing; Sergey Afanasyev: Software and Data curation; Kristoffer Alnes Røyset: Methodology, Writing – review & editing; Tina Søfteland: Writing – review & editing; Hege Lund: Conceptualization, Writing – review & editing, Supervision; Preben Boysen: Conceptualization, Writing – review & editing, Supervision, Project administration and Funding acquisition; Aleksei Krasnov: Conceptualization, Methodology, Writing – original draft preparation, Writing – review & editing, Project administration and Funding acquisition, All authors have read and agreed to the published version of the manuscript.Effect of two constant light regimens on antibody profiles and immune gene expression in atlantic salmon following vaccination and experimental challenge with salmonid alphavirus
