NK cells from peripheral blood of breast cancer patients and healthy donors that were expanded ex vivo exhibited similar expansion, phenotype, and cytotoxicity against breast cancer cell lines, and prevented tumor growth in a xenograft metastatic triple-negative breast cancer mouse model. Patient-expanded NK cells were cytotoxic against both autologous and allogeneic tumor cells in vitro.
BACKGROUND: Natural killer (NK) cells play a critical role in cancer immunosurveillance. Recent developments in NK cell ex-vivo expansion makes it possible to generate millions of activated NK cells from a small volume of peripheral blood. We tested the functionality of ex vivo expanded NK cells in vitro against breast cancer cell lines and in vivo using a xenograft mouse model. The study aim was to assess functionality and phenotype of expanded NK cells from breast cancer patients against breast cancer cell lines and autologous primary tumours. METHODS: We used a well-established NK cell co-culture system to expand NK cells ex vivo from healthy donors and breast cancer patients and examined their surface marker expression. Moreover, we tested the ability of expanded NK cells to lyse the triple negative breast cancer and HER2-positive breast cancer cell lines MDA-MB-231 and MDA-MB-453, respectively. We also tested their ability to prevent tumour growth in vivo using a xenograft mouse model. Finally, we tested the cytotoxicity of expanded NK cells against autologous and allogeneic primary breast cancer tumours in vitro. RESULTS: After 3 weeks of culture we observed over 1000-fold expansion of NK cells isolated from either breast cancer patients or healthy donors. We also showed that the phenotype of expanded NK cells is comparable between those from healthy donors and cancer patients. Moreover, our results confirm the ability of ex vivo expanded NK cells to lyse tumour cell lines in vitro. While the cell lines examined had differential sensitivity to NK cell killing we found this was correlated with level of major histocompatibility complex (MHC) class I expression. In our in vivo model, NK cells prevented tumour establishment and growth in immunocompromised mice. Finally, we showed that NK cells expanded from the peripheral blood of breast cancer patients show high cytotoxicity against allogeneic and autologous patient-derived tumour cells in vitro. CONCLUSION: NK cells from breast cancer patients can be expanded similarly to those from healthy donors, have a high cytotoxic ability against breast cancer cell lines and patient-derived tumour cells, and can be compatible with current cancer treatments to restore NK cell function in cancer patients.
Author Info: (1) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (2) Department
Author Info: (1) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (2) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (3) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (4) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (5) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (6) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (7) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (8) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (9) Cellular Therapy and Cancer Immunology Program, Department of Hematology/Oncology and BMT, Nationwide Children's Hospital, The Ohio State University Comprehensive Cancer Center, Ohio, USA. (10) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. (11) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. Department of Oncology, McMaster University, Hamilton, ON, Canada. (12) Department of Oncology, McMaster University, Hamilton, ON, Canada. (13) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada. ashkara@mcmaster.ca.
