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, School of Cancer Sciences, College of Medical Sciences and Dentistry, University of Birmingham.

Email: c.desanto@bham.ac.uk

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 stimulate 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), Professor Gary Middleton (lung and colorectal cancer), and Professor Paul Moss (haematological malignancies).

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

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 leukaemia creates an arginase-dependent immunosuppressive microenvironment. Blood. 2013 Jun 3. [Epub ahead of print]

Francis Mussai*, Carmela De Santo*,Vincenzo Cerundolo. 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.

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. 2011 Nov;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. Cancer research 2009 Dec 15;69(24):937684.

De Santo C , Salio M, Masri SH, Lee LY, Dong T, Speak AO, Porubsky S, Booth S, Veerapen N, Besra GS, Gröne HJ, Platt FM, Zambon M, Cerundolo V. Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest. 2008 Dec;118(12):4036-48.

Barral P, Eckl-Dorna J, Harwood NE, De Santo C, Salio M, Illarionov P, Besra GS, Cerundolo V, Batista FD. B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8345-50. Epub 2008 Jun 11.

Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, Basso G, Brombacher F, Borrello I, Zanovello P, Bicciato S, Bronte V. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006 Oct;116(10):2777-90.

Bronte V, Cingarlini S, Marigo I, De Santo C, Gallina G, Dolcetti L, Ugel S, Peranzoni E, Mandruzzato S, Zanovello P. Leukocyte infiltration in cancer creates an unfavorable environment for antitumor immune responses: a novel target for therapeutic intervention. Immunol Invest. 2006;35(3-4):327-57. Review.

De Santo C, Serafini P, Marigo I, Dolcetti L, Bolla M, Del Soldato P, Melani C, Guiducci C, Colombo MP, Iezzi M, Musiani P, Zanovello P, Bronte V. Nitroaspirin corrects immune dysfunction in tumor -bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4185-90. Epub 2005 Mar 7.

De Palma R, Marigo I, Del Galdo F, De Santo C, Serafini P, Cingarlini S, Tüting T, Lenz J, Basso G, Milan G, Zanovello P, Bronte V. Therapeutic effectiveness of recombinant cancer vaccines is associated with a prevalent T-cell receptor alpha usage by melanoma-specific CD8+ T lymphocytes. Cancer Res. 2004 Nov 1;64(21):8068-76.

*co-first authors