Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Nayoung Kim, Hong Kwan Kim, Kyungjong Lee, Yourae Hong, Jong Ho Cho, Jung Won Choi, Jung-Il Lee, Yeon-Lim Suh, Bo Mi Ku, Hye Hyeon Eum, Soyean Choi, Yoon-La Choi, Je-Gun Joung, Woong-Yang Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn () and Hae-Ock Lee ()
Additional contact information
Nayoung Kim: Samsung Medical Center
Hong Kwan Kim: Sungkyunkwan University School of Medicine
Kyungjong Lee: Sungkyunkwan University School of Medicine
Yourae Hong: Samsung Medical Center
Jong Ho Cho: Sungkyunkwan University School of Medicine
Jung Won Choi: Sungkyunkwan University School of Medicine
Jung-Il Lee: Sungkyunkwan University School of Medicine
Yeon-Lim Suh: Sungkyunkwan University School of Medicine
Bo Mi Ku: Sungkyunkwan University School of Medicine
Hye Hyeon Eum: Samsung Medical Center
Soyean Choi: Samsung Medical Center
Yoon-La Choi: Sungkyunkwan University
Je-Gun Joung: Samsung Medical Center
Woong-Yang Park: Samsung Medical Center
Hyun Ae Jung: Sungkyunkwan University School of Medicine
Jong-Mu Sun: Sungkyunkwan University School of Medicine
Se-Hoon Lee: Sungkyunkwan University School of Medicine
Jin Seok Ahn: Sungkyunkwan University School of Medicine
Keunchil Park: Sungkyunkwan University School of Medicine
Myung-Ju Ahn: Sungkyunkwan University School of Medicine
Hae-Ock Lee: Samsung Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

Date: 2020
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DOI: 10.1038/s41467-020-16164-1

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