Location of tumor affects local and distant immune cell type and number

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2017-03, Vol.5 (1), p.85-94
• Main Authors: Hensel, Jonathan A., Khattar, Vinayak, Ashton, Reading, Lee, Carnellia, Siegal, Gene P., Ponnazhagan, Selvarangan
• Format: Article
• Language: English
• Subjects: Animals; Bone marrow; Bone Neoplasms - immunology; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell culture; Cell Line, Tumor; Dendritic cells; Dendritic Cells - immunology; Experiments; Female; Flow cytometry; Ligands; macrophages; Macrophages - immunology; Metastasis; Mice, Inbred BALB C; Original Research; Spleen; Spleen - immunology; Tibia - immunology; Trends; tumor location; Tumor Microenvironment - immunology; Tumors; T‐cells
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.144

Introduction Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid‐derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. Methods In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia. In addition, immune cells from the spleen were examined from animals of both tumor locations by flow cytometry. Results The study demonstrates that location of tumor, and not simply the tumor itself, has a definitive role in regulating immune effectors. Among all immune cells characterized, macrophages were decreased and myeloid dendritic cell were increased in both tumor locations. This difference was more evident in subcutaneous tumors. Additionally, spleens from mice with subcutaneous tumors contained greater increases in both macrophages and myeloid dendritic cells than in mice with bone tumors. Furthermore, in subcutaneous tumors there was an increase in CD4+ and CD8+ T‐cell numbers, which was also observed in their spleens. Conclusions These data indicate that alterations in tumor‐reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone TME. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci. The data indicate that alterations in tumor‐reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone tumor microenvironment. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci.