Single-cell RNA sequencing of lung adenocarcinoma reveals heterogeneity of immune response-related genes

Ke Yue Ma, Alexandra A. Schonnesen, Amy Brock, Carla Vandenberg, S Gail Eckhardt, Zhihua Liu, Ning Jiang

Research output: Contribution to journalArticle

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Abstract

Immunotherapy has emerged as a promising approach to treat cancer. However, partial responses across multiple clinical trials support the significance of characterizing intertumor and intratumor heterogeneity to achieve better clinical results and as potential tools in selecting patients for different types of cancer immunotherapies. Yet, the type of heterogeneity that informs clinical outcome and patient selection has not been fully explored. In particular, the lack of characterization of immune response-related genes in cancer cells hinders the further development of metrics to select and optimize immunotherapy. Therefore, we analyzed single-cell RNA-Seq data from lung adenocarcinoma patients and cell lines to characterize the intratumor heterogeneity of immune response-related genes and demonstrated their potential impact on the efficacy of immunotherapy. We discovered that IFN-γ signaling pathway genes are heterogeneously expressed and coregulated with other genes in single cancer cells, including MHC class II (MHCII) genes. The downregulation of genes in IFN-γ signaling pathways in cell lines corresponds to an acquired resistance phenotype. Moreover, analysis of 2 groups of tumor-restricted antigens, namely neoantigens and cancer testis antigens, revealed heterogeneity in their expression in single cells. These analyses provide a rationale for applying multiantigen combinatorial therapies to prevent tumor escape and establish a basis for future development of prognostic metrics based on intratumor heterogeneity.

Original languageEnglish (US)
JournalJCI insight
Volume4
Issue number4
DOIs
StatePublished - Feb 21 2019

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RNA Sequence Analysis
Immunotherapy
Genes
Tumor Escape
Cell Line
Neoplasms
MHC Class II Genes
Neoplasm Genes
Testicular Neoplasms
Neoplasm Antigens
Patient Selection
Down-Regulation
Clinical Trials
RNA
Phenotype
Antigens
Adenocarcinoma of lung

Keywords

  • Bioinformatics
  • Immunology
  • Immunotherapy
  • Oncology

Cite this

Single-cell RNA sequencing of lung adenocarcinoma reveals heterogeneity of immune response-related genes. / Ma, Ke Yue; Schonnesen, Alexandra A.; Brock, Amy; Vandenberg, Carla; Eckhardt, S Gail; Liu, Zhihua; Jiang, Ning.

In: JCI insight, Vol. 4, No. 4, 21.02.2019.

Research output: Contribution to journalArticle

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AU - Jiang, Ning

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