Role: Junior PI
Role: Assistant Professor of General Pathology and Immunology
SCOPUS Author ID
Marinos Kallikourdis read Natural Sciences in Trinity College, Cambridge (UK) under the supervision of M.S. Neuberger, where he also received a PhD in Immunology for work done in the MRC Laboratory of Molecular Biology (Cambridge, UK) in the group of A.G. Betz. He was part of the team that first demonstrated the requirement for regulatory T cells in the sustenance of maternal-fetal tolerance and deciphered the mechanism of pregnancy-associated amelioration of Rheumatoid Arthritis. After a short post-doc in the MRC-LMB and at Istituto Clinico Humanitas, he became a junior Principal Investigator in Humanitas and Assistant Professor of General Pathology and Immunology in the Department of Medical Biotechnology and Translational Medicine, University of Milan. In 2015 he became Assistant Professor of General Pathology and Immunology at Humanitas University.
His work has received so far 1367 citations (5/2016, Scopus).
The main function of the adaptive immune system (composed of T cells and B cells) is to defend the self against pathogens. Simultaneously, via their ability to specifically recognize antigens, T cells are also used to define the identity of the self, whether genetically inherited or acquired during the individual’s lifespan via induced tolerance. Utilizing these mechanisms, mammals have successfully survived and evolved for tens of millions of years, with individuals dying soon after the end of their reproductively active age. Yet only in the last couple of centuries, human lifespan has expanded substantially beyond the reproductively active age. This is likely to create problems, as the information-processing capabilities of T cells have not been selected for dealing with the conditions found in aging tissues. This suggests that the interaction of adaptive immunity with different forms of pathology (cancer, cardiovascular, neurodegenerative disease) may be more complex than previously thought. Our lab is interested in deciphering these interactions at a molecular level and utilizing the findings to propose innovative therapeutic strategies.
Identifying the molecular mechanisms that mediate these interactions is often impeded by different factors: as the mechanisms involved lie at an intersection of different fields of study, some reductionist experimental systems can hide important variables. Key parameters are also often missed out as the metaphors that we commonly use to describe immune cell behavior can misguide us into attributing functions that have not been experimentally demonstrated. Keeping this analysis in mind, we study how T cell dynamic behavior and responses affect the development of pathology. The range of pathologies we study, aided by a robust network of specialized collaborations, includes immunodeficiency (WHIM syndrome), cancer, cardiovascular disease as well as neurological disorders such as amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disease. We make use (when it is efficacious) of techniques such as retrogenic technology and 2-photon microscopy. We then apply our findings to develop innovative solutions for the treatment of these pathologies, as proof-of-principle for eventual translation to the clinic.
Our work has received extensive support from the CARIPLO Foundation, the Veronesi Foundation, AIRC, the Ministry of Health, the Ministry of Education, Universities and Research, Telethon and AriSLA.
Adaptive immunity in Cancer
Garetto S, Sardi C, Martini E, Roselli G, Morone D, Angioni R, Cianciotti BC, Trovato AE, Franchina DG, Castino GF, Vignali D, Erreni M, Marchesi F, Rumio C and Kallikourdis M* (2016) Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model. Oncotarget (in press) doi: 10.18632/oncotarget.9280. (*:corresponding author)
Garetto S, Sardi C, Morone D and Kallikourdis M* Chemokines and T cell trafficking into tumors. Strategies to enhance recruitment of T cells into tumors. Book Chapter in Springer Volume: Defects in T cell Trafficking and Resistance to Cancer, edited by Emmanuel Donnadieu (in press) (*:corresponding author)
Adaptive immunity in Cardiovascular Diseases
Garetto S, Trovato AE, Sala F, Lleo A, Martini E, Betz AG, Norata GD, Invernizzi P and Kallikourdis M* (2015) Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment. Immunobiology 220(8), 1025-1029. doi: 10.1016/j.imbio.2015.02.006. (*:corresponding author)
Adaptive immunity in Neurological Diseases
Tortarolo M, Vallarola A, Lidonicci D, Battaglia E, Gensano F, Spaltro G, Fiordaliso F, Corbelli A, Garetto S, Martini E, Pasetto L, Kallikourdis M, Bonetto V and Bendotti C (2015) Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression. Journal of Neurochemistry. 135(1): 109-24. doi: 10.1111/jnc.13154
Adaptive Immunity (general)
Kallikourdis M, Trovato AE, Roselli G, Muscolini M, Porciello N, Tuosto L and Viola A. Phosphatidylinositol 4-phosphate 5-kinase β controls recruitment of lipid rafts into the immunological synapse (2016) J Immunol 196:1955. doi: 10.4049/jimmunol.1501788
Kallikourdis M, Viola A and Benvenuti F (2015) Human immunodeficiencies related to defective APC/T cell interaction. Front. Immunol. 6:433. doi: 10.3389/fimmu.2015.00433
Kallikourdis M(*), Trovato AE, Anselmi F, Sarukhan A, Roselli G, Tassone L, Badolato R and Viola A (2013) The CXCR4 mutations in WHIM syndrome impair the stability of the T cell immunological synapse. Blood 2013;122:666-73. (*:corresponding author)
Pregnancy, Adaptive Immunity and the Immunological Self
Benedusi V, Martini E, Kallikourdis M, Villa A, Meda C and Maggi A (2015) Ovariectomy shortens the life span of female mice. Oncotarget 6(13), 10801-10811.
Suano AM*, Kallikourdis M*, Sarris M* and Betz AG, (2012) Regulatory T cells protect from autoimmune arthritis during pregnancy, J Autoimmunity 38, J103-8. (*=contributed equally)
Terness P, Kallikourdis M, Betz AG, Rabinovich GA, Saito S & Clark DA (2007) Tolerance signaling molecules and pregnancy: IDO, galectins, and the renaissance of regulatory T cells. Am J Reprod Immunol 58, 238-254.
Kallikourdis M, Betz AG (2007) Periodic Accumulation of Regulatory T Cells in the Uterus; Preparation for the Implantation of a Semi-Allogeneic Fetus? PLoS ONE 2, e382.
Kallikourdis M, Andersen K, Welch K & Betz AG (2007) Alloantigen-Enhanced Accumulation of CCR5+ ‘Effector’ Regulatory T Cells in the Gravid Uterus. Proc Natl Acad Sci U S A 104, 594-599.
Aluvihare VR, Kallikourdis M & Betz AG (2005) Tolerance, Suppression and the Fetal Allograft. J Mol Med 83, 88-96.
Aluvihare V, Kallikourdis M & Betz A (2004) Regulatory T Cells Mediate Maternal Tolerance to the Fetus. Nat Immunol 5, 266-271.
Bystry RS, Aluvihare V, Welch KA, Kallikourdis M & Betz AG (2001) B Cells and Professional APCs Recruit Regulatory T Cells Via CCL4. Nat Immunol 2, 1126-1132.