IRB Seminar - Marinos Kallikourdis
Istituto di ricerca in biomedicina
Data: 10 Luglio 2017 / 12:00
Integrating the unexpected roles of T cells in cardiovascular and oncological pathology
Marinos Kallikourdis
Assistant Professor of Immunology and General Pathology, Humanitas University, Milan, Italy
Group Leader, Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Milan, Italy
IRB Seminar Room
Institute for Research in Biomedicine (IRB)
Via Vincenzo Vela 6
CH-6500 Bellinzona
Abstract
The adaptive immune system (composed of T cells and B cells) evolved in vertebrates, permitting the defense of the self against pathogens. Yet the evolution of mammalian pregnancy, and the associated recognition and active tolerization of paternally-derived fetal antigens during placental pregnancy, may have brought about key changes in the ability of the adaptive immune system to define and defend the self, in a manner optimized up to but not beyond the reproductively active age of the female (Aluvihare, Kallikourdis and Betz, Nature Immunology 2004). However, 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 adaptive immunity may not have been selected for dealing with the conditions found in aging tissues, when many of the above major diseases have their first incidence.
As an example of the application of the above rationale, we have recently demonstrated that pro-inflammatory T cells, which are used therapeutically to treat tumors, may be simultaneously mediating pro-tumoral effects (Garetto et al., Oncotarget 2016). The identification and deciphering of this unexpected effect may pave the way for the refinement of current immunotherapeutic strategies for cancer.
In an even more recent study, we identified, via immunophenotyping at different stages of the disease, an association between the presence of T cells and heart failure (HF), both in experimental models and in human HF patient biopsies. On the basis of this finding, we then utilized an FDA-approved drug that interferes with T cell function in order to treat experimentally-induced HF. Treatment resulted in a block of progression of HF, in a manner substantially more efficient than current standard drugs targeting cardiac disease (Kallikourdis et al, Nature Communications 2017).
