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

Commun Biol. 2021 Mar 9;4(1):314. doi: 10.1038/s42003-021-01842-7.

Abstract

Small 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cell Lineage
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, MHC Class I
  • Humans
  • Immunophenotyping
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Mice
  • Neuroendocrine Tumors / drug therapy
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / immunology
  • Neuroendocrine Tumors / pathology
  • Phenotype
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / immunology
  • Small Cell Lung Carcinoma / pathology
  • Transcriptome*
  • Tumor Microenvironment
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor