Yamei Zhao1, Xiaoxu Ge2, Xiaoming Xu3, Shaojun Yu1, Jian Wang4, Lifeng Sun5. 1. Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China. 2. Department of Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China. 3. Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China. 4. Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China. wangjian519@zju.edu.cn. 5. Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, People's Republic of China. sunlifeng@zju.edu.cn.
Abstract
BACKGROUND: The role of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remains controversial. This is especially so because the prognostic significance and clinicopathological relevance of different subtypes of TAMs in the immune microenvironment of CRC have not yet been established. OBJECTIVE: To assess the clinicopathological and prognostic value of pan-macrophages, M1-macrophages or M2-macrophages in patients with CRC. METHODS: Comprehensive searched on the Medline/PubMed, Web of Science (WoS) and Google Scholar databases was conducted to identify relevant studies published up to April 2019. The association between overall survival (OS), cancer-specific survival (CSS) or disease-free survival (DFS) and TAMs was analysed by meta-analysis. RESULTS: A total of 3749 patients from 17 studies were included. The pooled hazard ratios (HRs) indicated that high-density pan-macrophages improved OS (HR 0.67, P = 0.02). The pooled HR for M2-macrophages showed that high M2-macrophages infiltration was significantly associated with shorter OS (HR 2.93, P < 0.0001) and DFS (HR 2.04, P = 0.02). The pooled odds ratios (ORs) revealed that high-density TAMs was associated with high CD8+ T cell infiltration (OR 2.04, P = 0.007), no distant metastasis (NDM) (OR 0.38, P < 0.0001), microsatellite instability-high (MSI-H) (OR 0.38, P = 0.001), no lymph node metastasis (NLNM) (OR 0.54, P = 0.0002) and non-mucinous cancer (OR 0.39, P < 0.00001). CONCLUSIONS: Unlike other solid tumours, high-density CD68+ macrophage infiltration can be a good prognostic marker for CRC. However, when macrophages act as targets of combination therapy in CRC treatment, this might be more effective for CRC patients with high CD8+ T cell infiltrate, NDM, MSI-H, NLNM and non-mucinous cancer.
BACKGROUND: The role of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remains controversial. This is especially so because the prognostic significance and clinicopathological relevance of different subtypes of TAMs in the immune microenvironment of CRC have not yet been established. OBJECTIVE: To assess the clinicopathological and prognostic value of pan-macrophages, M1-macrophages or M2-macrophages in patients with CRC. METHODS: Comprehensive searched on the Medline/PubMed, Web of Science (WoS) and Google Scholar databases was conducted to identify relevant studies published up to April 2019. The association between overall survival (OS), cancer-specific survival (CSS) or disease-free survival (DFS) and TAMs was analysed by meta-analysis. RESULTS: A total of 3749 patients from 17 studies were included. The pooled hazard ratios (HRs) indicated that high-density pan-macrophages improved OS (HR 0.67, P = 0.02). The pooled HR for M2-macrophages showed that high M2-macrophages infiltration was significantly associated with shorter OS (HR 2.93, P < 0.0001) and DFS (HR 2.04, P = 0.02). The pooled odds ratios (ORs) revealed that high-density TAMs was associated with high CD8+ T cell infiltration (OR 2.04, P = 0.007), no distant metastasis (NDM) (OR 0.38, P < 0.0001), microsatellite instability-high (MSI-H) (OR 0.38, P = 0.001), no lymph node metastasis (NLNM) (OR 0.54, P = 0.0002) and non-mucinous cancer (OR 0.39, P < 0.00001). CONCLUSIONS: Unlike other solid tumours, high-density CD68+ macrophage infiltration can be a good prognostic marker for CRC. However, when macrophages act as targets of combination therapy in CRC treatment, this might be more effective for CRCpatients with high CD8+ T cell infiltrate, NDM, MSI-H, NLNM and non-mucinous cancer.
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