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Citations to this article

Immunosurveillance and therapy of multiple myeloma are CD226 dependent
Camille Guillerey, … , Mark J. Smyth, Ludovic Martinet
Camille Guillerey, … , Mark J. Smyth, Ludovic Martinet
Published April 20, 2015
Citation Information: J Clin Invest. 2015;125(5):2077-2089. https://doi.org/10.1172/JCI77181.
View: Text | PDF | Corrigendum
Research Article Immunology Oncology Article has an altmetric score of 24

Immunosurveillance and therapy of multiple myeloma are CD226 dependent

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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.

Authors

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

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 Total
Citations: 3 8 6 8 10 11 7 7 6 7 4 77
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (7)

Title and authors Publication Year
Targeting natural killer cells in cancer immunotherapy
C Guillerey, ND Huntington, MJ Smyth
Nature Immunology 2016
Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma
RE Cooke, NA Gherardin, SJ Harrison, H Quach, DI Godfrey, M Prince, R Koldej, DS Ritchie
Journal of Translational Medicine 2016
MGUS to myeloma: a mysterious gammopathy of underexplored significance
MV Dhodapkar
Blood 2016
Immunosurveillance and immunotherapy of tumors by innate immune cells
A Iannello, TW Thompson, M Ardolino, A Marcus, DH Raulet
Current Opinion in Immunology 2016
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia
M Boyiadzis, MR Bishop, R Abonour, KC Anderson, SM Ansell, D Avigan, L Barbarotta, AJ Barrett, KV Besien, PL Bergsagel, I Borrello, J Brody, J Brufsky, M Cairo, A Chari, A Cohen, J Cortes, SJ Forman, JW Friedberg, EJ Fuchs, SD Gore, S Jagannath, BS Kahl, J Kline, JN Kochenderfer, LW Kwak, R Levy, M Lima, MR Litzow, A Mahindra, J Miller, NC Munshi, RZ Orlowski, JM Pagel, DL Porter, SJ Russell, K Schwartz, MA Shipp, D Siegel, RM Stone, MS Tallman, JM Timmerman, FV Rhee, EK Waller, A Welsh, M Werner, PH Wiernik, MV Dhodapkar
Journal for ImmunoTherapy of Cancer 2016
Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies
C Guillerey, K Nakamura, S Vuckovic, GR Hill, MJ Smyth
Cellular and Molecular Life Sciences 2016
Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells: role of cMYC-IRF4-miR-125b interplay
MP Abruzzese, MT Bilotta, C Fionda, A Zingoni, A Soriani, E Vulpis, C Borrelli, B Zitti, MT Petrucci, MR Ricciardi, R Molfetta, R Paolini, A Santoni, M Cippitelli
Journal of Hematology & Oncology 2016

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