Research Paper Advance Articles

Identification of JUN gene and cellular microenvironment in response to PD-1 blockade treatment in lung cancer patients via single-cell RNA sequencing

Yuxuan Wang1, *, , Tao Ran2, *, , Yunke Li3, , Lei Tian2, , Lifeng Yang2, , Zhidong Liu1, , Biao Yao2, ,

  • 1 No.2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China
  • 2 Department of Oncology, Tongren People’s Hospital, Tongren, Guizhou, China
  • 3 Beijing Digitf Biotechnology Co., Ltd, Beijing, China
* Co-first author

Received: December 7, 2023       Accepted: May 3, 2024       Published: June 13, 2024      

https://doi.org/10.18632/aging.205932
How to Cite

Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Exploring the molecular mechanisms of PD-1/PDL-1 blockade for non-small cell lung cancer (NSCLC) would facilitate understanding for tumor microenvironment (TME) and development of individualized medicine. To date, biomarkers of response to PD-1 blockade therapy were still limited. In this study, we hypothesize that cell type in the tumor microenvironment can influence the effect of PD-1 blockade immunotherapy through specific genes. Therefore, we re-analyze the single-cell RNA sequencing data and validation in tissue from lung adenocarcinoma patients. Dynamic changes of cellular subpopulation were observed after anti-PD-1 immunotherapy among TMEs between primary/metastasis or good/poor response patients. Non-exhausted CD8 T cells and dysregulated genes were observed in responsing patients from PD-1 blockade therapy. Among all changed genes, JUN, involved in PD-1 blockade immunotherapy pathway, and could be considered as a PD-1 responsing biomarker.

Abbreviations

LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; DEG: Differentially expressed gene; NSCLC: Non-small cell lung cancer; PD-1: Programmed cell death protein 1; PD-L1: Programmed cell death protein ligand 1; scRNASeq: Single-cell RNA sequencing; TPM: Transcripts Per Kilobase of exon model per Million mapped reads.