Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

Pengfei Zhang; Boxue He; Qidong Cai; Guangxu Tu; Xiong Peng; Zhenyu Zhao; Weilin Peng; Fenglei Yu; Min Wang; Yongguang Tao; Xiang Wang

doi:10.3389/fonc.2021.705888

Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity

Front Oncol. 2021 Sep 8:11:705888. doi: 10.3389/fonc.2021.705888. eCollection 2021.

Authors

Pengfei Zhang^{1

2}, Boxue He^{1

2}, Qidong Cai^{1

2}, Guangxu Tu^{1

2}, Xiong Peng^{1

2}, Zhenyu Zhao^{1

2}, Weilin Peng^{1

2}, Fenglei Yu^{1

2}, Min Wang³, Yongguang Tao^{1

2

4

5}, Xiang Wang^{1

2}

Affiliations

¹ Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, China.
² Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Second Xiangya Hospital, Central South University, Changsha, China.
³ Department of Laboratory Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
⁴ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
⁵ National Health Commission of the People's Republic of China (NHC), Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, China.

Abstract

Background: Lung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.

Methods: We analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.

Results: IL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.

Conclusion: The IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

Keywords: IL-6; NK cells; early lung adenocarcinoma; ground-glass opacities; tumor microenvironment.