Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma.
The Vk*MYC transgenic and transplant mouse models of multiple myeloma (MM) are well established as a research tool for anti-myeloma drug discovery. However, little is known of the immune response in these models. Understanding the immunological relevance of these models is of increasing importance as immunotherapeutic drugs are developed against MM.



We set out to examine how cellular immunity is affected in Vk*MYC mouse models and compare that to the immunology of patients with newly diagnosed and relapsed/refractory MM.



We found that there were significant immunological responses in mice developing either spontaneous (transgenic) or transplanted MM as a consequence of the degree of tumor burden. Particularly striking were the profound B cell lymphopenia and the expansion of CD8(+) effector memory T cells within the lymphocyte population that progressively developed with advancing disease burden, mirroring changes seen in human MM. High disease burden was also associated with increased inflammatory cytokine production by T lymphocytes, which is more fitting with relapsed/refractory MM in humans.



These findings have important implications for the application of this mouse model in the development of MM immunotherapies. Trial registration LitVacc ANZCTR trial ID ACTRN12613000344796; RevLite ANZCTR trial ID NCT00482261.
ACRF Translational Research Laboratory, Royal Melbourne Hospital, Parkville, VIC, 3010, Australia. rachel.cooke@mh.org.au.|Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia. rachel.cooke@mh.org.au.|Department of Medicine, University of Melbourne, Melbourne, Australia. rachel.cooke@mh.org.au.
Rachel E
0000-0001-5222-0433
RE
Cooke
Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia.|Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, 3010, Australia.
Nicholas A
NA
Gherardin
Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia.|Department of Medicine, University of Melbourne, Melbourne, Australia.
Simon J
SJ
Harrison
Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia.|Department of Medicine, University of Melbourne, Melbourne, Australia.
Hang
H
Quach
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia.
Dale I
DI
Godfrey
Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia.|Department of Medicine, University of Melbourne, Melbourne, Australia.
Miles
M
Prince
ACRF Translational Research Laboratory, Royal Melbourne Hospital, Parkville, VIC, 3010, Australia.|Department of Medicine, University of Melbourne, Melbourne, Australia.
Rachel
R
Koldej
ACRF Translational Research Laboratory, Royal Melbourne Hospital, Parkville, VIC, 3010, Australia.|Cancer Immunology Program, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC, 3002, Australia.|Department of Medicine, University of Melbourne, Melbourne, Australia.
David S
DS
Ritchie
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000378:metabolism; D008231:Lymphopenia / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D009368:Neoplasm Transplantation
D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators
CD8; IFNγ; Immunology; Microenvironment; Myeloma; TEM; Vk*MYC