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. 2023 Feb 27;43(2):BSR20221659.
doi: 10.1042/BSR20221659.

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients

Bin Yi  1   2   3 , Yuanda Cheng  1   2   3 , Ruimin Chang  1   2   3 , Wolong Zhou  1   2   3 , Huili Tang  1   2   3 , Yang Gao  1   2   3 , Chunfang Zhang  1   2   3
Affiliations

Prognostic significance of tumor-associated macrophages polarization markers in lung cancer: a pooled analysis of 5105 patients

Bin Yi et al. Biosci Rep. .

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.

Keywords: Tumor-associated macrophages; lung cancer; pooled analysis; prognosis.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Flow diagram of the studies’ selection
Figure 2
Figure 2. Forest plots comparing the survival of CD68+ TAMs in the tumor and TS for LCa patients
(A) HR of OS for CD68+ TAMs in the tumor; (B) HR of DFS for CD68+ TAMs in the tumor; (C) HR of OS for CD68+ TAMs in TS; (D) HR of DFS for CD68+ TAMs in TS. Abbreviations: DFS, disease-free survival; HR, hazard risk; LCa, lung cancer; OS, overall survival; TAMs, tumor-associated macrophages; TS, tumor stroma.
Figure 3
Figure 3. Forest plots comparing the survival of nest and TN/TS CD68+ TAMs for LCa patients
(A) HR of OS in raw data for CD68+ TAMs in TN; (B) HR of OS in raw data for TN/TS CD68+ TAMs; (C) HR of OS with adjusted measures for CD68+ TAMs in TN; (D) HR of OS with adjusted measures for TN/TS CD68+ TAMs. Abbreviations: HR, hazard risk; LCa, lung cancer; OS, overall survival; TAMs, tumor-associated macrophages; TN, tumor nest; TS, tumor stroma.
Figure 4
Figure 4. Forest plots comparing the survival of HLA-DR+ TAMs in TN and TS for LCa patients
(A) HR of OS for HLA-DR+ TAMs in TN; (B) HR of OS for HLA-DR+ TAMs in TS. Abbreviations: HR, hazard risk; LCa, lung cancer; OS, overall survival; TAMs, tumor-associated macrophages; TN, tumor nest; TS, tumor stroma.
Figure 5
Figure 5. Forest plots comparing the survival of CD204+ TAMs in TS for LCa patients
(A) HRs of OS in raw data for CD204+ TAMs in TS; (B) HRs of OS with adjusted measures for CD204+ TAMs in TS. Abbreviations: HR, hazard risk; LCa, lung cancer; OS, overall survival; TAMs, tumor-associated macrophages; TS, tumor stroma.
Figure 6
Figure 6. Forest plots comparing the survival of CD163+ TAMs in TN and TS for LCa patients
(A) HR of OS for CD163+ TAMs in TN; (B) HR of OS for CD163+ TAMs in TS. Abbreviations: HR, hazard risk; LCa, lung cancer; OS, overall survival; TAMs, tumor-associated macrophages; TN, tumor nest; TS, tumor stroma.
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