Dr Carmela De Santo

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Dr Carmela De Santo is an expert on tumour immunosuppression, and in particular on myeloid derived suppressor cells.
Position:

CRUK New Investigator Fellow, Institute of Immunology and Immunotherapy, College of Medical Sciences and Dentistry, University of Birmingham.

Email: c.desanto@bham.ac.uk

UofB profile

 

Background and Research focus

Following a degree in Biology at the University of Padua, Carmela joined Professor Vincenzo Bronte’s group in 2002 to study for a PhD. Her studies focussed on myeloid derived suppressor cells (MDSCs), a heterogeneous grouping of myeloid lineage cells that suppress immune responses, and which are emerging as a key immunoregulatory axis, both in the context of pathogen-specific immunity, and also tumour-specific immune responses. After successfully completing her PhD, she carried out post-doctoral studies in Professor Vincenzo Cerundolo’s laboratory in the Weatherall Institute for Molecular Medicine in Oxford, in 2006, where her research again focussed on MDSCs both in cancer and virus infection, and also investigated the ability of  invariant Natural Killer T cells to regulate MDSCs suppressive activity.

 

As one of the UK’s leading experts on MDSC function, Carmela’s current research focusses firstly on understanding the molecular mechanisms underpinning the MDSC-mediated immune suppression in the tumour microenvironment and to understand the mechanisms of cancer to promote a immunosuppressive microenvironment and create a immopriviledge niche.  These studies encompass a number of tumours, including Acute Myeloid Leukaemia, but also solid tumours including neuroblastoma, and lung cancer (as mesothelioma). A second focus is on investigating potential routes to therapeutically target MDSC function in the clinic, with the aim of developing novel immunotherapy strategies that stimulating anti-tumour immunity in cancer patients by depressing MDSC-mediated immunosuppression. Potential routes that Carmela is investigating include pharmacological inhibition of MDSC function, and use of invariant Natural Killer T cells to suppress MDSC effector functions. Carmela’s research programme benefits from strong collaborative interactions with CIIC group leaders in aligned clinical areas, in particular with Dr Francis Mussai (paediatric oncology) and Professor Gary Middleton (lung and colorectal cancer).

 

Expertise

Tumour microenvironment;  Immune suppression; immune regulation; myeloid derived suppressor cells (MDSCs); Natural Killer T cells (NKTs); functional assays; T cells; dendritic cells; myeloid differentiation; myeloid precursors.

 

Other activities

In addition to leading her own research group, Carmela is involved in public engagement activity, including taking part in laboratory tours for members of the public, and patients or patients’ relatives.

 

Publications

Khanna S, Graef S, Mussai F, Thomas A, Wali N, Yenidunya BG, Yuan CM, Morrow B, Zhang J, Korangy F, Greten TF, Steinberg SM, Stetler-Stevenson M, Middleton G, De Santo C*, Hassan R*. Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.  Clin Cancer Res. 2018 Mar 30. pii: clincanres.3757.2017. doi: 10.1158/1078-0432.CCR-17-3757*co-last authors

 

De Santo C, Booth S, Vardon A, Cousins A, Tubb V, Perry T, Noyvert B, Beggs A, Ng M, Halsey C, Kearns P, Cheng P, Mussai F. The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated-recombinant arginase I BCT-100.  Int J Cancer. 2018 Apr 1;142(7):1490-1502. doi: 10.1002/ijc.31170. Epub 2017 Dec 26.

 

Vardon A, Dandapani M, Cheng D, Cheng P, De Santo C, Mussai F. Arginine auxotrophic gene signature in paediatric sarcomas and brain tumours provides a viable target for arginine depletion therapies. Oncotarget. 2017 

 

Fultang L, Vardon A, De Santo C, Mussai F. Molecular basis and current strategies of therapeutic arginine depletion for cancer. 
Int J Cancer. 2016 Aug 1;139(3):501-9. doi: 10.1002/ijc.30051. Epub 2016 Apr 15.

 

De Santo C, Mussai F. Neuroblastoma arginine addiction subverts the anticancer immune response. Oncoimmunology. 2015 Nov 11;5(2):e1078967. eCollection 2016.

 

Mussai F, Egan S, Hunter S, Webber H, Fisher J, Wheat R, McConville C, Sbirkov Y, Wheeler K, Bendle G, Petrie K, Anderson J, Chesler L, De Santo C. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.Cancer Res. 2015 Aug 1;75(15):3043-53.

 

Mussai F, Egan S, Higginbotham-Jones J, Perry T, Beggs A, Odintsova E, Loke J, Pratt G, U KP, Lo A, Ng M, Kearns P, Cheng P, De Santo C. Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target. Blood. 2015 Apr 9;125(15):2386-96.

 

Mussai F*, De Santo C*, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P, Cerundolo V. Acute myeloid leukemia creates an arginase- dependent immunosuppressive microenvironment. Blood. 2013 Aug 1;122(5):749-58.. *co-first authors

 

Mussai F*, De Santo C*, Cerundolo V. Interaction Between Invariant NKT Cells and Myeloid-derived Suppressor Cells in Cancer Patients: Evidence and Therapeutic Opportunities Journal Immunotherapy. 2012 Jul;35(6):449-59. *co-first authors

 

De Santo C, Arscott R, Booth S, Karydis I, Jones M, Asher R, Salio M, Middleton M, Cerundolo V. Invariant NKT cells modulate the suppressive activity of Serum Amyloid A differentiated IL-10 secreting neutrophils Nat Immunol. 2011Nov;11(11):1039-46

Ugel S*, Zoso A*, De Santo C*, Li Y, Marigo I, Zanovello P, Scarselli E, Cipriani B, Oelke M, Schneck JP, Bronte V. In vivo administration of artificial antigenpresenting cells activates low- avidity T cells for treatment of cancer. Can Res 2009 Dec 15;69(24):937684. *co-first authors