Trial Lecture - time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Karin Tarte, Head of the Immunology and Cell Therapy Lab at Rennes University Hospital, Rennes, France
- Second opponent: Associate Professor Bengt Johansson Lindbom, Immunology Section, Lund University, Sweden
- Third member of the adjudication committee: Professor Bjørn Steen Skålhegg, Institute of Basic Medical Sciences, University of Oslo
Chair of the Defence
Professor Øyvind Bruland, Institute of Clinical Medicine, University of Oslo
Principal Supervisor
Associate Professor June H. Myklebust, Institute of Clinical Medicine, University of Oslo
Summary
Immune checkpoint blockade represents a breakthrough in cancer treatment. By the use of antibodies that block inhibitory receptors on T cells, the immune system's ability to kill cancer cells can be restored. So far, antibodies targeting PD-1 and CTLA-4 have been most explored and are now clinically approved for several cancer types.
In the thesis Role of immune checkpoint receptors in T cells from B-cell non-Hodgkin lymphoma tumors Sarah E. Josefsson and colleagues aimed to identify mechanisms for T-cell dysfunction and discover new targets for checkpoint blockade in B-cell non-Hodgkin lymphoma (NHL). By screening for inhibitory receptor expression using high dimensional flow cytometry, and characterizing T-cell function by studying T-cell receptor signaling and cytokine production, they discovered that dysfunctional T cells from follicular lymphoma tumors displayed high expression of the novel inhibitory receptor TIGIT. When extending these studies to other NHLs such as mantle cell lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia, they found that the majority of intratumoral effector T cells from all NHL types investigated expressed TIGIT, which was frequently co-expressed with PD-1. Josefsson et al. also investigated checkpoint receptor expression in regulatory T cells (Tregs). FOXP3+ Tregs are often enriched in NHL and considered a suppressive barrier to antitumor immunity. However, the impact of Treg density on disease outcome remains unclear, emphasizing the need for additional markers to identify truly suppressive cells. Here, flow cytometry was combined with unsupervised clustering, and revealed that distinct Treg subsets could be identified based on expression of OX40 and PD-1. This provided new insight into Treg heterogeneity in NHL. Importantly, all intratumoral Tregs expressed TIGIT. Together, the results presented in this thesis suggest TIGIT as a promising target for checkpoint blockade in NHL, potentially in co-blockade with PD-1.
Additional information
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