关键词: 结直肠癌, 自噬, 肿瘤相关巨噬细胞, LC3, 肿瘤微环境

Abstract: Background and purpose: Tumor immune escape has become the difficulty of immunotherapy. In colorectal cancer, active autophagy can increase antigen in tumor microcirculation and then induce anti-tumor immunity. This study aimed to detect the expressions of LC3, tumor-associated macrophage (TAM) and their products in colorectal cancer, and to explore the influence of LC3 on tumor microenvironment and its clinical significance. Methods: Immunohistochemical analysis was used to detect the expressions of LC3, CD16, CD163, CD4, CD8, CD20, CD68, IL-1, IL-10, TNF-α and TGF-β in colorectal cancer samples archived in the department of pathology, Binzhou Medical University Hospital and department of pathology, Binzhou Second People’s Hospital from Jan. 2013 to Dec. 2014, and their correlations with clinicopathological features and prognosis were analyzed. Results: The expressions of LC3, CD16 and CD163 were higher in colorectal cancer than in adjacent normal colon tissues (P<0.05). The expression of LC3 was positively correlated with the infiltration of M1 TAM, but negatively correlated with the infiltration of M2 TAM (P<0.05). The expressions of LC3 and M1 TAM were positively correlated with IL-1, TNF-α and the infiltration of CD4 ⁺ , CD8 ⁺ and CD20 ⁺ lymphocytes, while the expression of M2 TAM was positively correlated with IL-10 and TGF-β, but negatively correlated with the infiltration of CD4 ⁺ , CD8 ⁺ and CD20 ⁺ lymphocytes (P<0.05). The expressions of LC3, CD16 and CD163 were closely related to tumor size, invasion and lymph node metastasis (P<0.05). Kaplan-Meier and COX regression model analyses showed that the expression levels of LC3, CD16 and CD163 and lymph node metastasis were closely related to the prognosis of colorectal cancer patients, and were independent risk factors for the prognosis of colorectal cancer. Conclusion: The increase of autophagy in colorectal cancer can induce macrophage recruitment and polarization of TAM into M1 phenotype, and then induces immune cell aggregation. Regulating autophagy can be a new way to induce polarization of TAM and enhance anti-tumor immunity in colorectal cancer.

Key words: Colorectal cancer, Autophagy, Tumor-associated macrophage, LC3, Tumor microenvironment