Immunosurveillance and therapy of multiple myeloma are CD226 dependent

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

doi:10.1172/jci77181

Cited by 114 publications

(126 citation statements)

References 75 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…Student t test was performed to compare CXCR3 expression from CXCL10 low versus CXCL10 high patients. Ã , P < 0.05; ÃÃ , P < 0.01. confirming recent observations (37). Noteworthy, our results show that multiple myeloma growth determines a decreased trafficking capacity of KLRG1 À NK cells to bone marrow due to significant changes in the expression levels of several chemokines.…”

Section: Klrg1supporting

confidence: 92%

Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment

et al. 2015

View full text Add to dashboard Cite

show abstract

Section: Klrg1supporting

confidence: 92%

Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The lack of any inflammatory T cell response in transplant Vk#4929 might be explained by the fact that it is a very aggressive clone that causes rampant extramedullary disease and may not allow time for the usual immune aberrancies to develop. In line with this observation, another group described CD8 + T lymphopenia developing in mice transplanted with an aggressive Vk*MYC clone (mice needed to be culled by 5 weeks post-transplant) [35]. There is also the suggestion that inflammation wanes with end-stage disease [35] or is replaced by a Th2 response [19].…”

Section: Discussionmentioning

confidence: 96%

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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

show abstract

“…CD226 was recently implicated in immune surveillance in a transgenic multiple myeloma mouse model 142 . When the multiple myeloma transgenic mice were crossed with Cd226-deficient mice, spontaneous development of multiple myeloma was reduced.…”

Section: Tigit and Pvr Family Membersmentioning

confidence: 99%

Combination cancer immunotherapy and new immunomodulatory targets

Mahoney

Rennert²,

Freeman

2015

Nat Rev Drug Discov

1,124

907

View full text Add to dashboard Cite

Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.

show abstract

Immunosurveillance and therapy of multiple myeloma are CD226 dependent

Cited by 114 publications

References 75 publications

Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment

Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma

Combination cancer immunotherapy and new immunomodulatory targets

Contact Info

Product

Resources

About