Research Paper|Volume 16, Issue 12|pp 10348—10365

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

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

* Co-first author

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

https://doi.org/10.18632/aging.205932

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.