Evangelos Giampazolias Cancer Immunosurveillance - Evangelos Giampazolias

Dr Evangelos Giampazolias

Evangelos Giampazolias received his BSc in Chemistry (2009) and MSc in Clinical Biochemistry (2012) from the University of Athens in Greece. In 2012, he moved to Glasgow, UK, for his PhD at the CRUK Beatson Institute under the supervision of Professor Stephen Tait. During his PhD, he discovered the pro-inflammatory signals that accompany caspase-independent cell death and their impact on cancer immunity. For this, he was awarded the Institute of Cancer Sciences Prize (2017) and the CRUK Pontecorvo Prize (2018). Evangelos subsequently joined the group of Professor Caetano Reis e Sousa at the Francis Crick Institute in London, UK, as a Postdoctoral Fellow. There, he identified that the plasma actin-scavenging system promotes cancer immune escape by hijacking innate immune mechanisms of dead cell sensing in the tumour microenvironment. He was recently granted an innovation patent (2020) to explore the therapeutic potential of these findings as novel immunotherapies for cancers. In 2023, Evangelos will establish the Cancer Immunosurveillance group at the CRUK Manchester Institute, which will focus on the characterisation of the fundamental mechanisms that enable the immune system to recognise and respond to cancer through sensing and integration of cues that are elicited by dying cells and commensal microbes.

Introduction

The immune system comprises a natural defensive mechanism with remarkable sensitivity and specificity in discriminating between the cells of the tumour and their normal cell counterparts. Cells of the adaptive immunity called T cells are often the spearhead of anti-cancer immunity. Although T cell-based immunotherapies have dramatically improved clinical outcomes, clinical benefit is limited to a small fraction of patients with cancer. Instruction of T cell immunity is a key function of dendritic cells (DC). Like other innate immune cells, DCs express a wide repertoire of receptors endowing them with the ability to detect microbial presence and tissue damage. How these functions contribute to anti-cancer immunity remains unclear but dying cancer cells and certain commensal bacterial taxa have been linked to induction of cancer-specific T cells and enhanced responses to immunotherapy. 

In the Cancer Immunosurveillance laboratory, we focus on two fundamental pillars of host physiology, cell death and microbes, that trigger and shape adaptive anti-cancer immune responses under the umbrella of innate immunity. To achieve this, we combine genetically modified mouse models and tumour engineering to disentangle complex tumour-host interactions that underpin cancer immunity.  

The scientific interest of the Cancer Immunosurveillance research group


We have previously identified components of host physiology (caspases and secreted gelsolin) that inhibit cancer-specific T cell immunity by acting as natural barriers to innate immune sensing of dying tumour cells. We are currently studying anti-cancer immunity as a function of host factors that tune the composition and immunogenicity of gut commensals. 

Using our previously established models, we aim to define the mechanisms that enable DCs to sense (1) dying cancer cells and (2) commensal microbes and understand how they integrate such cues to elicit robust T cell immunity against cancer. Our ultimate vision is to contribute to the basic understanding of cancer immunity and pave way for therapeutic approaches to overcome immunotherapy resistance.

Selected Publications

Giampazolias E, Schulz O, Lim KHJ, Rogers NC, Chakravarty P, Srinivasan N, Gordon O, Cardoso A, Buck MD, Poirier EZ, Canton J, Zelenay S, Sammicheli S, Moncaut N, Varsani-Brown S, Rosewell I, Reis e Sousa C. (2021)
Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity.
Cell 184(15):4016-4031.e22. PubMed abstract (PMID: 34081922)


Tunbak H, Enriquez-Gasca R, Tie CHC, Gould PA, Mlcochova P, Gupta RK, Fernandes L, Holt J, van der Veen AG, Giampazolias E, Burns KH, Maillard PV & Rowe HM. (2020)
The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s. 
Nature Communications 11, 5387: 1-15. PubMed abstract (PMID: 33144593)


Minutti CM, Modak RV, Macdonald F, Li F, Smyth DJ, Dorward DA, Blair N, Husovsky C, Muir A, Giampazolias E, Dobie R, Maizels R, Kendall TJ, Griggs DW, Kopf M, Henderson NC, Zaiss DM. (2019)
A macrophage-pericyte axis directs tissue restoration via Amphiregulin-induced TGFβ activation. 
Immunity 50: 645-654. PubMed abstract (PMID: 30770250)


Giampazolias E, Tait SW. (2018)
Caspase-independent cell death: an anti-cancer double-whammy. 
Cell Cycle 17(3):269-270. PubMed abstract (PMID: 29169278)


Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C, Cao K, Roca A, Lopez J, Ichim G, Proïcs E, Rubio-Patiño C, Fort L, Yatim N, Woodham E, Orozco S, Taraborrelli L, Peltzer N, Lecis D, Machesky L, Walczak H, Albert M, Milling S, Oberst A, Ricci JE, Ryan KM, Blyth K, Tait SW. (2017)
Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency.
Nature Cell Biology 19(9): 1116-1129. PubMed abstract (PMID: 28846096)


Woodham E, Paul N, Tyrrell B, Spence H, Swaminathan K, Scribner M, Giampazolias E, Hedley A, Clark W, Kage, F, Marston DJ, Hahn KM, Tait, SWG, Larue L, Brakebusch, CH, Insall, RH, Machesky, LM. (2017)
Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. 
Current Biology 27: 624-637. PubMed abstract (PMID: 28238662)


Lopez J, Bessou M, Riley JS, Giampazolias E, Todt F, Rochegüe T, Oberst A, Green DR, Edlich F, Ichim G, Tait SW. (2016)
Mito-priming as a method to engineer Bcl-2 addiction. 
Nature Communications 7, 10538: 1-11. PubMed abstract (PMID: 26833356)


Giampazolias E, Tait SW. (2016)
Mitochondria and the hallmarks of cancer. 
FEBS Journal 283(5): 803-14. PubMed abstract (PMID: 26607558)


Ichim G, Lopez J, Ahmed SU, Muthalagu N, Giampazolias E, Delgado ME, Haller M, Riley JS, Mason SM, Athineos D, Parsons MJ, van de Kooij B, Bouchier-Hayes L, Chalmers AJ, Rooswinkel RW, Oberst A, Blyth K, Rehm M, Murphy DJ, Tait SW. (2015)
Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. 
Molecular Cell 57(5): 860-72. PubMed abstract (PMID: 25702873)


Haller M, Hock AK, Giampazolias E, Oberst A, Green DR, Debnath J, Ryan KM, Vousden KH, Tait SW. (2014) 
Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity. 
Autophagy 10(12): 2269-78. PubMed abstract (PMID: 25629932)

 

Scientific Officer
TBA in January 2023

Graduate Student
TBA in January 2023

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