Impact of the immune molecular profile of the tumor microenvironment on the prognosis of NSCLC

Hangjie Ying; Qingqing Hang; Guoping Cheng; Shifeng Yang; Xiaojing Lai; Min Fang

doi:10.3892/ol.2023.13717

Impact of the immune molecular profile of the tumor microenvironment on the prognosis of NSCLC

Oncol Lett. 2023 Feb 14;25(3):131. doi: 10.3892/ol.2023.13717. eCollection 2023 Mar.

Authors

Hangjie Ying^{1

2}, Qingqing Hang³, Guoping Cheng^{2

4}, Shifeng Yang^{2

4}, Xiaojing Lai^{2

5}, Min Fang^{2

5}

Affiliations

¹ Zhejiang Cancer Institute, The Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, P.R. China.
² Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China.
³ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
⁴ Department of Pathology, The Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, P.R. China.
⁵ Key Laboratory of Radiation Oncology of Zhejiang Province, Department of Thoracic Radiotherapy, The Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, P.R. China.

Abstract

The present study aimed to clarify the association between macrophages, tumor neo-vessels and programmed cell death-ligand 1 (PD-L1) in the tumor microenvironment and the clinicopathological features of patients with non-small cell lung cancer (NSCLC), and to explore the prognostic factors of stromal features in NSCLC. To determine this, tissue microarrays containing samples of 92 patients with NSCLC were studied using immunohistochemistry and immunofluorescence. The quantitative data demonstrated that in tumor islets, the number of CD68⁺ and CD206⁺ tumor-associated macrophages (TAMs) was 8-348 (median, 131) and 2-220 (median, 52), respectively (P<0.001). In tumor stroma, the number of CD68⁺ and CD206⁺ TAMs was 23-412 (median, 169) and 7-358 (median, 81), respectively (P<0.001). The number of CD68⁺ TAMs in each location of the tumor islets and tumor stroma was significantly higher than that of CD206⁺ TAMs, and they were significantly correlated (P<0.0001). The quantitative density of CD105 and PD-L1 in tumor tissues was 19-368 (median, 156) and 9-493 (median, 103), respectively. Survival analysis revealed that a high density of CD68⁺ TAMs in tumor stroma and islets and a high density of CD206⁺ TAMs and PD-L1 in tumor stroma were associated with worse prognosis (both P<0.05). Collectively, the survival analysis demonstrated that the high-density group was related to a worse prognosis regardless of combined neo-vessels and PD-L1 expression with the CD68⁺ TAMs in tumor islets and stroma, or CD206⁺ TAMs in tumor islets and stroma. To the best of our knowledge, the present study was the first to provide a multi-component combined prognostic survival analysis of different types of macrophages in different regions with tumor neo-vessels and PD-L1, which demonstrated the importance of macrophages in tumor stroma.

Keywords: macrophage; non-small cell lung cancer; programmed cell death 1-ligand 1; tumor stroma.

Grants and funding

This research was supported by the grants of The National Natural Science Foundation of China (grant no. 81703018) and The Zhejiang Medical and Health Science and Technology Project (grant nos. 2020KY466 and 2022RC110), both to MF.