Dr Santiago Zelenay

Santiago Zelenay – Research summary

Santiago Zelenay

Santiago Zelenay

The extent to which the immune system acts as a natural barrier to cancer has been a subject of debate. This notion has recently gained great support from the remarkable clinical success of therapies aimed at exploiting cells from the immune system. Yet, whether and how tumours trigger and simultaneously evade the immune system are longstanding questions in cancer biology. Our group investigates the mechanisms underlying natural and therapy-induced tumour immunity with a particular emphasis on identifying the cellular and molecular mediators that regulate the balance between tumour-suppressive versus tumour-promoting inflammation.

Inflammatory cells present at the tumour site are known for promoting several key aspects of carcinogenesis. At the same time, effective anti-tumour immunity depends on inflammatory mediators that contribute to the activation of innate immune cells such as dendritic cells. Combining the use of genetically engineered cancer models with the analysis of samples from cancer patients, we aim at identifying the underlying mechanisms that allow evasion of immune control and enable progressive tumour growth. In this context, main objectives of the group are to elucidate the signals that trigger innate immune cell activation initiating tumour immunity and to distinguish mediators favouring tumour elimination from those that support cancer progression. This distinction should allow stratifying subgroups of cancer patients with an immune promoting tumour environment likely to benefit from existing immunotherapy from those with active pathways resulting in local immune inhibition. The ultimate goal of the group is to develop novel targeted interventions to disrupt immune suppression, promote tumour immunity and enhance the efficacy of cancer therapy.

People

Santiago Zelenay – People

Eduardo Bonavita (Postdoctoral Fellows)
Victoria Pelly (Postdoctoral Fellows)
Eimear Flanagan (PhD Student)
Charlotte Bell (PhD Student)
Christian Bromley (PhD Student)

People

Santiago Zelenay – People

Eduardo Bonavita (Postdoctoral Fellows)
Victoria Pelly (Postdoctoral Fellows)
Eimear Flanagan (PhD Student)
Charlotte Bell (PhD Student)
Christian Bromley (PhD Student)

Biography

Santiago Zelenay obtained his degree in Biology from the University of Buenos Aires in 2002. As an undergraduate student he worked in DNA vaccines in the laboratory of Juan Fló. He then undertook his PhD in Immunology at the Institute Gulbenkian of Science in Portugal where he studied regulatory T cells, working with Jocelyne Demengeot and Antonio Coutinho. In 2008, he joined the group of Caetano Reis e Sousa at the CRUK London Research Institute, where he was awarded Marie Curie and EMBO long-term postdoctoral fellowships to investigate innate immune receptors and signalling pathways that trigger dendritic cell activation and drive T cell responses against viruses or tumours. Since 2015, Santiago leads the Cancer Inflammation and Immunity Group at the Cancer Research UK Manchester Institute, which focuses on understanding the underlying mechanisms that mediate cancer-inhibitory versus tumour-promoting inflammation in order to design new therapies for cancer patients.

Publications

  • Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, and Reis e Sousa C. 2018. NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control. Cell. doi:10.1016/j.cell.2018.01.004.
  • Bonavita E, Pelly VS, and Zelenay S. 2018. Resolving the dark side of therapy-driven cancer cell death. J Exp Med. 215:9-11. doi:10.1084/jem.20172044.
  • Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popović B, Bernardini G, Magrini E, Gianni F, Zelenay S, Jonjić S, Santoni A, Garlanda C, and Mantovani A. 2017. IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity. Nature. 551:110-114. doi:10.1038/nature24293.
  • Zelenay S, van der Veen AG, Böttcher JP, Snelgrove KJ, Rogers N, Acton SP, Chakravarty P, Girotti MR, Marais R, Quezada SA, Sahai E, Reis e Sousa C. 2015. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell. 162(6):1257-70.
  • Helft J, Böttcher J, Chakravarty P, Zelenay S, Huotari J, Schraml BU, Goubau D, Reis e Sousa C. 2015. GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells. Immunity. 42(6):1197-211.
  • Schraml BU, van Blijswijk J, Zelenay S, Whitney PG, Filby A, Acton SE, Rogers NC, Moncaut N, Carvajal JJ, and Reis e Sousa C. 2013. Genetic Tracing via DNGR-1 Expression History Defines Dendritic Cells as a Hematopoietic Lineage. Cell 154(4):843–858.
  • Zelenay S and Reis e Sousa C. 2013. Adaptive immunity after cell death. Trends Immunol 34(7):329–335.
  • Zelenay S, Keller AM, Whitney PG, Schraml BU, Deddouche S, Rogers NC, Schulz O, Sancho D, and Reis e Sousa C. 2012. The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice. J Clin Invest 122(5):1615–1627.
  • Ahrens S, Zelenay S, Sancho D, Hanč P, Kjær S, Feest C, Fletcher G, et al. 2012. F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36(4):635–645.
  • Zelenay S, Bergman M-L, Paiva RS, Lino AC, Martins AC, Duarte JH, Moraes Fontes MF, Bilate AM, Lafaille JJ, and Demengeot J. 2010. Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization. J Immunol 185(7):3829–3833.
  • Duarte JH, Zelenay S, Bergman M-L, Martins AC, and Demengeot J. 2009. Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur J Immunol 39(4):948–955.
  • Zelenay S, Chora A, Soares MP, and Demengeot J. 2007. Heme oxygenase-1 is not required for mouse regulatory T cell development and function. Int Immunol 19(1):11–18.
  • Zelenay S, Lopes-Carvalho T, Caramalho I, Moraes-Fontes MF, Rebelo M, and Demengeot J. 2005. Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc Natl Acad Sci USA 102(11):4091–4096.
  • Zelenay S, Elías F, and Fló J. 2003. Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides. Eur J Immunol 33(5):1382–1392.