Journal article

Immunosurveillance and therapy of multiple myeloma are CD226 dependent

Camille Guillerey, Lucas Ferrari de Andrade, Slavica Vuckovic, Kim Miles, Shin Foong Ngiow, Michelle CR Yong, Michele WL Teng, Marco Colonna, David S Ritchie, Martha Chesi, P Leif Bergsagel, Geoffrey R Hil, Mark J Smyth, Ludovic Martinet

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2015

Abstract

Multiple myeloma (MM) is an age-dependent hematological malignancy. Evaluation of immune interactions that drive MM relies on in vitro experiments that do not reflect the complex cellular stroma involved in MM pathogenesis. Here we used Vk*MYC transgenic mice, which spontaneously develop MM, and demonstrated that the immune system plays a critical role in the control of MM progression and the response to treatment. We monitored Vk*MYC mice that had been crossed with Cd226 mutant mice over a period of 3 years and found that CD226 limits spontaneous MM development. The CD226-dependent anti-myeloma immune response against transplanted Vk*MYC MM cells was mediated both by NK and CD8+ T cells thr..

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Grants

Awarded by National Health and Medical Research Council (NH&MRC) of Australia


Awarded by NHMRC Australia


Awarded by ARC cancer research foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

The authors wish to thank Liam Town, Kate Elder, Joanne Sutton, and Shellie Brown for breeding, genotyping, maintenance, and care of the mice used in this study. We thank Christopher Chan, Ricky Johnstone, and members of his group for providing the original Vk*MYC breeding pairs and helpful discussions. We thank Leesa Wockner for helpful advice concerning the statistical analysis of the data. L. Martinet and D.S. Ritchie were supported by a National Health and Medical Research Council (NH&MRC) of Australia Project grant (1044392). M.J. Smyth and L. Ferrari de Andrade were supported by a NH&MRC Australia Fellowship (628623) and Program Grant (1013667). L. Martinet was supported by the ARC cancer research foundation (PDF20140601127).