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Myeloid derived suppressor cells and macrophages in regulation of immune response in cancer and tumor progression
In-person only
Myeloid cells represent a major component of the tumor microenvironment (TME) and are critically involved in the regulation of tumor progression and metastasis. In recent years, the overarching concept has emerged that the biology of myeloid cells is largely defined by a limited number of functional states that transcend the narrowly defined cell populations. These functional states are primarily centred around classical and pathological states of activation, with the latter state being commonly defined as myeloid-derived suppressor cells (MDSC). I will discuss recent data defining these states of activation of granulocytes in the kinetic of tumor progression. Ferroptosis – programmed cell death triggered in cells with impaired redox regulation whereby excessive availability/activity of redox-active iron primarily due to defect in glutathione peroxidase 4/glutathione (GPX4/GSH) system. The active ROS/RNS-generating machinery of polymorphonuclear MDSC (PMN-MDSC) in tumors shattered redox balance and stimulated a ferroptotosis. Ferroptotic PMN-MDSC demonstrated potent immune suppressive activity. Ferroptotic PMN-MDSC released lipid peroxidation products that directly suppress T-cell function. Treatment of immune competent tumor-bearing mice with ferroptosis inhibitor had anti-tumor activity and the effect of immunotherapy was substantially enhanced. I will discuss general approaches to therapeutic targeting of myeloid cells.
Date:
17 June 2024, 12:00
Venue:
Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details:
Lecture Theatre
Speaker:
Prof Dmitry Gabrilovich (Chief Scientist, Cancer Immunology, AstraZeneca)
Organising department:
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)
Organiser:
Doris Chan (Kennedy Institute of Rheumatology)
Organiser contact email address:
doris.chan@kennedy.ox.ac.uk
Host:
Professor Irina Udalova (Kennedy Institute of Rheumatology)
Part of:
Kennedy Institute Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Doris Chan
