Understanding the crosstalk between γδ T cells and osteoclasts in patients with breast cancer
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1
ACTREC-TMC, India
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2
Tata Memorial Hospital, India
Bone metastasis is a common cause of morbidity in breast cancer patients. Aminobisphosphonates are widely used in treatment of bone metastasis and skeletal disorders. Aminobisphosphonates increase endogenous pool of isopentenyl pyrophosphate (IPP) of mevalonate pathway in tumor cells, which acts as potent antigen for γδ T cells. γδ T cells are unique subsets of T-lymphocytes that are activated by aminobisphosphonates and phosphoantigens (bromohydrin pyrophosphate, IPP). The present study aims at understanding the crosstalk between γδ T cells and osteoclasts in patients with breast cancer metastasis. Multicolor flow cytometry showed higher expression of RANKL on γδ T cells of breast cancer patients. Stimulation with aminobisphosphonate (zoledronate) increased RANKL expression on γδ T cells. Osteoclasts generated from CD14+ monocytes of breast cancer patients and healthy individuals in the presence of zoledronate activated γδ T cells showed reduced osteoclastogenesis as analysed by 23c6 mAb (CD51/61) and DAPI staining. Osteoclasts generated in the presence of cell free supernatants of activated γδ T cells showed reduced resorption area (pits) on Osteoclast Activity Assay Substrate. Cytokine analysis of activated γδ T cells showed presence of IFN-γ, antiosteoclastogenic cytokine. Zoledronate activated γδ T cells have high propensity to migrate to bone and inhibit osteoclastogenesis. Aminobisphosphonate activated γδ T cell based immunotherapy would be a promising approach to treat bone metastasis in breast cancer.
Keywords:
Aminobisphosphonates,
γδ T cells,
Osteoclasts,
bone metastasis,
breast cancer
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Chiplunkar
S,
Phalke
SP,
Parmar
V and
Badwe
RA
(2013). Understanding the crosstalk between γδ T cells and osteoclasts in patients with breast cancer.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01017
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Received:
30 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Shubhada Chiplunkar, ACTREC-TMC, Navi Mumbai, Maharashtra, 410210, India, schiplunkar@actrec.gov.in