Age-related macrophage alterations are associated with carcinogenesis of colorectal cancer

Author:

Li Yinuo1,Zhao Yahui1,Gao Yang1,Li Yu1,Liu Mei1,Xu Ningzhi1,Zhu Hongxia1ORCID

Affiliation:

1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing,100021 , China

Abstract

Abstract Older age is a major risk factor for colorectal cancer. Macrophage is one of the most abundant immune cell types infiltrated in colorectal cancer, but the contribution of macrophages in elder tumor microenvironment is far from clear. In this study, we first detected the expression of CD206, CD68 in colorectal cancer tissues by multiplex fluorescence immunohistochemical staining. The infiltration of CD68+/CD206+ cells in tumor tissues from old patients was higher than those from young patients. When mixed with CT26 cells, both young and aged TAMs enhanced tumor growth of CT26 cells, but CT26 mixed with aged TAMs form larger tumors compared with young TAMs. CT26 formed more and larger tumors in the abdominal cavity of aged mice compared with young. Total macrophage infiltration and the CD206+ macrophages infiltration were both higher in aged mice compared with young mice. The expression signatures of tumor-associated macrophages altered with ageing and p-NF-κB translocation to nucleus was more significant in TAMs from aged mice compared with young. Our results showed that infiltration of macrophages in colorectal cancer tissues increased with ageing. Macrophages from aged host were more likely to polarize to pro-tumor phenotype, and more powerful in promoting tumor cell proliferation.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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