Prognostic Significance of Tumor-associated Macrophages Polarization Markers in Lung Cancer: a Pooled Analysis of 5105 Patients

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2023 Jan 12

PMID 36633963

Authors

Bin Yi

Yuanda Cheng

Ruimin Chang

Wolong Zhou

Huili Tang

Yang Gao

Chunfang Zhang

Affiliations

Soon will be listed here.

Abstract

Background: The prognostic significance of tumor-associated macrophages (TAMs) in patients with lung cancer (LCa) remains controversial. We therefore conducted the present study to systematically evaluate the role of different TAMs markers and histologic locations on the prognosis of LCa.

Methods: Searches of Web of Science, PubMed, and EMBASE databases were performed up to 28 February 2022. The pooled analysis was conducted in random-effect or fixed-effects model with hazard risk (HR) and 95% confidence interval (CI) for survival data including overall survival (OS), and disease-free survival (DFS) from raw or adjusted measures, according to different TAMs markers and histologic locations.

Results: Including a total of 5105 patients from 30 eligible studies, the results indicated that the total count of CD68+ TAMs was negatively associated with OS and DFS, which was also observed in the relationship of CD68+ or CD204+ TAMs in tumor stroma (TS) with OS and DFS (all P<0.05). Conversely, higher CD68+ TAMs density in tumor nest (TN) or TN/TS ratio of CD68+ TAMs predicted better OS (all P<0.05). Similarly, higher HLA-DR+ TAMs density was correlated with better OS in TN and TS (all P<0.05). Besides, neither nest CD163+ TAM density nor stromal CD163+ TAM density was a prognostic factor in LCa patients (all P>0.05).

Conclusion: Our study indicated that different TAMs markers and histologic locations could bring about different prognostic effects in LCa patients. Great understanding of the infiltration modes of TAMs may contribute to improve outcomes of LCa patients.

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References

Chen J, Yao P, Yuan A, Hong T, Shun C, Kuo M . Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res. 2003; 9(2):729-37. View

Zhang B, Yao G, Zhang Y, Gao J, Yang B, Rao Z . M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics (Sao Paulo). 2011; 66(11):1879-86. PMC: 3203959. DOI: 10.1590/s1807-59322011001100006. View

Eerola A, Soini Y, Paakko P . Tumour infiltrating lymphocytes in relation to tumour angiogenesis, apoptosis and prognosis in patients with large cell lung carcinoma. Lung Cancer. 1999; 26(2):73-83. DOI: 10.1016/s0169-5002(99)00072-0. View

Zheng X, Weigert A, Reu S, Guenther S, Mansouri S, Bassaly B . Spatial Density and Distribution of Tumor-Associated Macrophages Predict Survival in Non-Small Cell Lung Carcinoma. Cancer Res. 2020; 80(20):4414-4425. DOI: 10.1158/0008-5472.CAN-20-0069. View

Altman D, Bland J . How to obtain the confidence interval from a P value. BMJ. 2011; 343:d2090. DOI: 10.1136/bmj.d2090. View

Tang X, Mo C, Wang Y, Wei D, Xiao H . Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology. 2012; 138(2):93-104. PMC: 3575762. DOI: 10.1111/imm.12023. View

Takanami I, Takeuchi K, Kodaira S . Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis. Oncology. 1999; 57(2):138-42. DOI: 10.1159/000012021. View

Mantovani A, Sozzani S, Locati M, Allavena P, Sica A . Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002; 23(11):549-55. DOI: 10.1016/s1471-4906(02)02302-5. View

Hwang I, Kim J, Ylaya K, Chung E, Kitano H, Perry C . Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients. J Transl Med. 2020; 18(1):443. PMC: 7686699. DOI: 10.1186/s12967-020-02618-z. View

10.

Li W, Zhang X, Wu F, Zhou Y, Bao Z, Li H . Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer. Cell Death Dis. 2019; 10(12):918. PMC: 6892854. DOI: 10.1038/s41419-019-2131-y. View

11.

Dai F, Liu L, Che G, Yu N, Pu Q, Zhang S . The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer. BMC Cancer. 2010; 10:220. PMC: 2880994. DOI: 10.1186/1471-2407-10-220. View

12.

Meador C, Sequist L, Piotrowska Z . Targeting Exon 20 Insertions in Non-Small Cell Lung Cancer: Recent Advances and Clinical Updates. Cancer Discov. 2021; 11(9):2145-2157. PMC: 8673432. DOI: 10.1158/2159-8290.CD-21-0226. View

13.

Amemiya R, Miyoshi T, Aokage K, Suzuki J, Hoshino H, Udagawa H . Prognostic impact of the tumor immune microenvironment in pulmonary pleomorphic carcinoma. Lung Cancer. 2021; 153:56-65. DOI: 10.1016/j.lungcan.2021.01.007. View

14.

Mansuet-Lupo A, Alifano M, Pecuchet N, Biton J, Becht E, Goc J . Intratumoral Immune Cell Densities Are Associated with Lung Adenocarcinoma Gene Alterations. Am J Respir Crit Care Med. 2016; 194(11):1403-1412. DOI: 10.1164/rccm.201510-2031OC. View

15.

Kim D, Min H, Lee K, Kim Y, Oh D, Jeon Y . High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer. Br J Cancer. 2008; 98(6):1118-24. PMC: 2275476. DOI: 10.1038/sj.bjc.6604256. View

16.

Feng P, Yu C, Wu C, Lee M, Lee W, Wang L . Tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery. Am J Transl Res. 2014; 6(5):593-603. PMC: 4212933. View

17.

Li Y, Sun B, Pei B, Li C, Zhang Z, Yin Y . Osteopontin-expressing macrophages in non-small cell lung cancer predict survival. Ann Thorac Surg. 2015; 99(4):1140-8. DOI: 10.1016/j.athoracsur.2014.11.054. View

18.

Rami-Porta R . Future Perspectives on the TNM Staging for Lung Cancer. Cancers (Basel). 2021; 13(8). PMC: 8074056. DOI: 10.3390/cancers13081940. View

19.

Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T . Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008; 113(6):1387-95. DOI: 10.1002/cncr.23712. View

20.

Petty A, Yang Y . Tumor-associated macrophages: implications in cancer immunotherapy. Immunotherapy. 2017; 9(3):289-302. PMC: 5619052. DOI: 10.2217/imt-2016-0135. View