Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov 12:10:10.

Lysis of aminobisphosphonate-sensitized MCF-7 breast tumor cells by Vγ9Vδ2 T cells

Swati Dhar  1 , Shubhada V Chiplunkar
Affiliations

Lysis of aminobisphosphonate-sensitized MCF-7 breast tumor cells by Vγ9Vδ2 T cells

Swati Dhar et al. Cancer Immun. .

Abstract

Aminobisphosphonates are drugs administered for the treatment of bone resorption. They can indirectly activate peripheral γδ T cells and render tumor cells susceptible to lysis by Vγ9Vδ2 T cells. We have investigated the molecules involved in conjugate formation and killing of aminobisphosphonate-treated MCF-7 breast tumor cells by Vγ9Vδ2 T cells. Lysis of aminobisphosphonate (Pamidronate and Zoledronate)-treated MCF-7 tumor cells by Vγ9Vδ2 T cells was assessed by chromium release assays and time-lapse video microscopy. MCF-7 breast cancer cells were chosen as aminobisphosphonates are employed to alleviate bone resorption in this malignancy. Cell cycle profile and expression of MICA, ICAM-I and FasL on aminobisphosphonate-sensitized MCF-7 breast tumor cells was confirmed by flow cytometry. Involvement of γδ TCR and NKG2D in mediating cytotoxicity of aminobisphosphonate-treated MCF-7 breast tumor cells by Vγ9Vδ2 T cells was assessed using blocking antibodies in chromium release assays. MCF-7 tumor cells pretreated with Pamidronate and Zoledronate were efficiently lysed by Vγ9Vδ2 T cells. Pamidronate and Zoledronate treatment of MCF-7 cells induced S phase arrest and did not alter expression of MICA, ICAM-I and FasL. Blocking γδ TCR and NKG2D on Vγ9Vδ2 T cells inhibited lysis of Pamidronate and Zoledronate-treated MCF-7 cells. Inhibiting the perforin-granzyme pathway in Vγ9Vδ2 T cells using concanamycin A reduced their ability to lyse aminobisphosphonate-treated MCF-7 cells. Vγ9Vδ2 T cells form strong conjugates with aminobisphosphonate-treated MCF-7 breast tumor cells. γδ TCR, NKG2D and perforin-granzyme pathway are involved in the lysis of MCF-7 breast tumor cells treated with aminobisphosphonates by Vγ9Vδ2 T cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
Figure 6
Figure 6
Figure 7
Figure 7
Figure 8
Figure 8
See this image and copyright information in PMC

References

    1. Thedrez A, Sabourin C, Gertner J, Devilder MC, Allain-Maillet S, Fournie JJ, Scotet E, Bonneville M. Self/non-self discrimination by human gammadelta T cells: simple solutions for a complex issue? Immunol Rev. 2007;215:123–135. - PubMed
    1. Green JR. Antitumor effects of bisphosphonates. Cancer. 2003;97:840–847. - PubMed
    1. Kunzmann V, Bauer E, Wilhelm M. Gamma/delta T-cell stimulation by pamidronate. N Engl J Med. 1999;340:737–738. - PubMed
    1. Dieli F, Gebbia N, Poccia F, Caccamo N, Montesano C, Fulfaro F, Arcara C, Valerio MR, Meraviglia S, Di Sano C, Sireci G, Salerno A. Induction of gammadelta T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo. Blood. 2003;102:2310–2311. - PubMed
    1. Bouet-Toussaint F, Cabillic F, Toutirais O, Le Gallo M, Thomas de la Pintière C, Daniel P, Genetet N, Meunier B, Dupont-Bierre E, Boudjema K, Catros V. Vgamma9Vdelta2 T cell-mediated recognition of human solid tumors. Potential for immunotherapy of hepatocellular and colorectal carcinomas. Cancer Immunol Immunother. 2008;57:531–539. - PMC - PubMed

Publication types

LinkOut - more resources