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The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis

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Abstract

Purpose

There is a growing literature on the significance of tumor-associated macrophages (TAMs) in colorectal cancer (CRC). However, the role of TAMs in predicting the prognosis of CRC remains controversial. The current study aims to determine the prognostic and clinicopathological value of different types and distribution of TAMs in CRC.

Methods

A comprehensive literature search of PubMed, Embase, and Cochrane Library databases was conducted from the inception to 1 September 2019. The correlations of TAMs with overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and clinicopathological characteristics were analyzed.

Results

A total of 5,575 patients from 29 studies were included in this meta-analysis. The pooled hazard ratios (HRs) indicated that high density of pan-macrophages in tumor invasive margin (IM) was associated with better OS (HR = 0.57, 95%CI = 0.38–0.85), DFS (HR = 0.32, 95%CI = 0.19–0.52), and CSS (HR = 0.56, 95%CI = 0.41–0.77). Moreover, the high density of pan-macrophages in tumor center (TC) was correlated with better DFS (HR = 0.66, 95%CI = 0.45–0.96). However, high expression of M2 macrophages in TC was associated with poor DFS (HR = 2.42, 95%CI = 1.45–4.07) and CSS (HR = 1.74, 95%CI = 1.24–2.44). High M2 macrophages density in IM was also associated with short DFS (HR = 2.81, 95%CI = 1.65–4.77). In addition, the results showed that high density of pan-macrophages in IM was associated with no tumor metastasis, while high M2 macrophages density in TC was correlated with poor tumor differentiation.

Conclusion

High Pan-TAMs density in IM has a positive effect on the prognosis of CRC patients, while high density M2 macrophage infiltration in TC is a strong indicator of poor prognosis.

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Funding

The work was supported by the National Basic Research Program of China (973 program, J.L., Grant #2015CB932600), the National Natural Science Foundation of China (J.L., No. 81472735); Wuhan University (J.L., 2042019kf0206).

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Author notes

  1. Zhenwei Yang and Mengna Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Zhenwei Yang, Mengna Zhang, Ruyi Peng, Jialong Liu, Fan Wang, Yizhang Li, Qiu Zhao & Jing Liu

  2. Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China

    Zhenwei Yang, Mengna Zhang, Ruyi Peng, Jialong Liu, Fan Wang, Yizhang Li, Qiu Zhao & Jing Liu

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  1. Zhenwei Yang
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Contributions

All the authors designed the study. Data were collected by Zhenwei Yang, Mengna Zhang, Ruyi Peng, and Jialong Liu. Quality control of data was performed by Fan Wang and Yizhang Li. All authors analyzed the data. Zhenwei Yang and Mengna Zhang wrote the first draft of article. All authors revised the article and approved the final version.

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Correspondence to Jing Liu.

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ESM 1

Forest plots after excluding studies that TAMs are from regional lymph node. A, CD68 TAMs and OS in tumor invasion margin; B, CD68 TAMs and CSS in tumor invasion margin. (PNG 164 kb).

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ESM 2

Completed 2009 PRISMA Checklist. (DOCX 29 kb).

ESM 3

(DOCX 14 kb).

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Yang, Z., Zhang, M., Peng, R. et al. The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis 35, 1651–1661 (2020). https://doi.org/10.1007/s00384-020-03686-9

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