Immunosurveillance and therapy of multiple myeloma are CD226 dependent

Guillerey, Camille, de Andrade, Lucas Ferrari, Vuckovic, Slavica, Miles, Kim, Ngiow, Shin Foong, Yong, Michelle C. R., Teng, Michele W. L., Colonna, Marco, Ritchie, David S., Chesi, Martha, Bergsagel, P. Leif, Hill, Geoffrey R., Smyth, Mark J. and Martinet, Ludovic (2015) Immunosurveillance and therapy of multiple myeloma are CD226 dependent. Journal of Clinical Investigation, 125 5: 2077-2089. doi:10.1172/JCI77181

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Author Guillerey, Camille
de Andrade, Lucas Ferrari
Vuckovic, Slavica
Miles, Kim
Ngiow, Shin Foong
Yong, Michelle C. R.
Teng, Michele W. L.
Colonna, Marco
Ritchie, David S.
Chesi, Martha
Bergsagel, P. Leif
Hill, Geoffrey R.
Smyth, Mark J.
Martinet, Ludovic
Title Immunosurveillance and therapy of multiple myeloma are CD226 dependent
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 1558-8238
0021-9738
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1172/JCI77181
Open Access Status File (Author Post-print)
Volume 125
Issue 5
Start page 2077
End page 2089
Total pages 13
Place of publication Ann Arbor, MI United States
Publisher American Society for Clinical Investigation
Collection year 2016
Language eng
Formatted 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 through perforin and IFN-γ pathways. Moreover, CD226 expression was required for optimal antimyeloma efficacy of cyclophosphamide (CTX) and bortezomib (Btz), which are both standardly used to manage MM in patients. Activation of costimulatory receptor CD137 with mAb (4-1BB) exerted strong antimyeloma activity, while inhibition of coinhibitory receptors PD-1 and CTLA-4 had no effect. Taken together, the results of this study provide in vivo evidence that CD226 is important for MM immunosurveillance and indicate that specific immune components should be targeted for optimal MM treatment efficacy. As progressive immunosuppression associates with MM development, strategies aimed to increase immune functions may have important therapeutic implications in MM.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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