The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma

Aims: The role of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumour-infiltrating lymphocytes (TILs) and prognosis in CRC by the use of image analysis. Methods and results: Immunohistochemical staining for CD68 and CD163 was performed as pan-macrophage and M2-macrophage markers, respectively. Each marker was analysed separately for intra-epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (P = 0.001). Intra-epithelial CD68⁺ macrophage densities showed a correlation with pTNM stage (P = 0.008), microsatellite instability (MSI) (P < 0.001), CpG island methylator phenotype (CIMP) (P < 0.001) and TIL densities (P < 0.001). Intra-epithelial CD163⁺ macrophage densities were associated with perineural invasion, MSI, CIMP and TIL densities (P < 0.001). Stromal CD68⁺ and CD163⁺ macrophage densities had a significant relationship with intra-epithelial and stromal CD3⁺ (P = 0.001 and P < 0.001, respectively) and CD8⁺ (P < 0.001) T cells. High intra-epithelial CD68⁺ macrophage density was associated with worse overall survival (HR = 1.386, 95% CI = 1.043–1.843, P = 0.025) and progression-free survival (HR = 1.522, 95% CI = 1.146–2.020, P = 0.004). Intra-epithelial CD68⁺ macrophage density was also an independent prognostic factor of the progression-free survival (HR = 1.447, 95% CI = 1.076–1.947, P = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions and TIL densities. Conclusion: Our results indicate that the density of intratumoural macrophages is a useful prognostic indicator for further stratifying T cell populations in CRC.