Myeloid cells infiltrating tumor microenvironment orchestrate immune response to induce cancer progression. From tumor cell proliferation to angiogenesis, invasion, and metastasis, every step of cancer development is controlled by distinct types of immune cells. Tumor-associated macrophages (TAMs), myeloid derived suppressor cells (MDSCs), TIE2-expressing monocytes (TEMs), tumor associated neutrophils (TANs), and sub-population of dendritic cells are examples of tumor promoting myeloid cells. These numerous types of myeloid cells have been identified and characterized but their spatial organization within the tumor microenvironment have not been analyzed thoroughly. To understand their actions and mechanisms on cancer promotion, understanding their organization is required. By using EL4 thymoma syngenic graft model, we analyzed composition of myeloid cells infiltrating EL4 tumor microenvironment and revealed spatial organization of each type of myeloid cells. Dozens of immune cell surface markers were used to comprehensively define and characterize tumor infiltrating myeloid cells. Most of CD11b positive myeloid cells were localized at surrounding matrix of tumor mass. In particular, immunosuppressive immune cells like MDSCs were localized surrounding matrix of tumor and barely infiltrating actual tumor mass. In contrast, TAMs and dendritic cells are integrated with tumor cells inside the tumor mass. Dendritic cells can be subdivided based on CD11b expression level and those two distinct subsets are localized at distinct area of tumor mass. This analysis of spatial localization of immune cells implies division of labor among the cancer promoting myeloid cells. Tumor mass integrated myeloid cells suspected to promote angiogenesis and tumor cell proliferation. Tumor surrounding matrix localized myeloid cells suspected to promote immune suppression, invasion and metastasis.
Citation Format: Minhyeok Kim, Seon Woo Lee, Suk-Jo Kang, Changwon Kang. Spatial organization of myeloid cells in tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A74.
- ©2015 American Association for Cancer Research.