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. 2024 Apr 24;44(4):BSR20231194.
doi: 10.1042/BSR20231194.

Prognostic and clinical significance of tumor-associated macrophages in esophageal squamous cell carcinoma after surgery: do biomarkers and distributions matter?

Bin Yi  1   2   3 , Jun Zeng  1   2   3 , Linfeng Li  1   2   3 , Junjie Zhang  1   2   3 , Yufan Chen  1   2   3 , Yang Gao  1   2   3
Affiliations

Prognostic and clinical significance of tumor-associated macrophages in esophageal squamous cell carcinoma after surgery: do biomarkers and distributions matter?

Bin Yi et al. Biosci Rep. .

Abstract

Background: The role of tumor-associated macrophages (TAMs) in patients with esophageal squamous cell carcinoma (ESCC) following surgery remains controversial. Hence, we performed the present study to systematically analyze the prognostic and clinical significance of distinct TAMs biomarkers and distributions in ESCC patients underwent surgery.

Methods: PubMed, Web of Science, and EMBASE databases were searched up to March 31, 2023. The pooled analysis was conducted to evaluate the effects of TAMs on overall survival (OS), disease-free survival (DFS), and clinicopathological characteristics using fixed-effects or random-effect model.

Results: Involving a total of 2,502 ESCC patients underwent surgery from 15 studies, the results suggested that the total count of CD68+ TAMs was inversely associated with OS and DFS in ESCC patients, which was also noticed in the relationship of CD68+ TAMs in tumor islet (TI) with OS (all P<0.05), although no association between CD68+ TAMs in tumor stroma (TS) and OS (P>0.05). Moreover, either islet or stromal CD163+ TAMs density was a prognostic factor ESCC (all P<0.05). Similarly, an elevated CD204+ TAMs density in TI predicted a poor DFS (P<0.05), although CD204+ TAMs in TI had no relationship with OS (P>0.05). Besides, a high CD68+ TAMs density was significantly associated with lymphatic vessel invasion, vascular invasion, and lymph node metastasis (all P<0.05).

Conclusion: Our results demonstrated the prognostic and clinical significance of TAMs in ESCC patients underwent surgery. TAMs should be considered a target that could improve prognostic stratification and clinical outcomes in ESCC after surgery.

Keywords: Clinical significance; Esophageal squamous cell carcinoma; Pooled analysis; Prognostic significance; Tumor-associated macrophages.

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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 article selection
Figure 2
Figure 2. Forest plots of HR for survival outcomes between high and low density of total CD68+ TAMs infiltration in the tumor among ESCC patients underwent surgery.
(A) HR of OS for total CD68+ TAMs in the tumor; (B) HR of DFS for total CD68+ TAMs in the tumor. DFS, disease-free survival; ESCC, esophageal squamous cell carcinoma; HR, hazard risk; OS, overall survival; TAM, tumor-associated macrophages.
Figure 3
Figure 3. Forest plots of HR for OS between high and low density of CD68+ TAMs in ESCC patients underwent surgery.
(A) HR of OS for CD68+ TAMs in TI; (B) HR of OS for CD68+ TAMs in TS. ESCC, esophageal squamous cell carcinoma; HR, hazard risk; OS, overall survival; TAM, tumor-associated macrophage; TI, tumor islet; TS, tumor stroma.
Figure 4
Figure 4. Forest plots of HR for OS between high and low density of CD163+ TAMs in ESCC patients underwent surgery.
(A) HR of OS for CD163+ TAMs in TI; (B) HR of OS for CD163+ TAMs in TS. ESCC, esophageal squamous cell carcinoma; HR, hazard risk; OS, overall survival; TAM, tumor-associated macrophage; TI, tumor islet; TS, tumor stroma.
Figure 5
Figure 5. Forest plots of HR for survival outcomes between high and low density of CD204+ TAMs in TI among ESCC patients underwent surgery.
(A) HR of OS for CD204+ TAMs in TI; (B) HR of DFS for CD204+ TAMs in TI. DFS, disease-free survival; ESCC, esophageal squamous cell carcinoma; HR, hazard risk; OS, overall survival; TAM, tumor-associated macrophage; TI, tumor islet.
Figure 6
Figure 6. Funnel plot of studies with TAM density for potential publication bias assessment.
(A) OS and CD68+ TAMs in the tumor; (B) OS and CD68+ TAMs in TI; (C) OS and CD68+ TAMs in TS. OS, overall survival; TAM, tumor-associated macrophage; TI, tumor islet; TS, tumor stroma.
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