Audun Kvalvaag contributes to articles in Science Immunology and Nature Immunology
Researcher Audun Kvalvaag at Department of Molecular Cell Biology (MCB) and Centre for Cancer Cell Reprogramming (CanCell) is a specialist on activation of cytotoxic T cells, and he has recently been involved in collaborations with Elliot Philips in Xiang-Peng Kong´s group at New York University Grossman School of Medicine, and with Pablo Céspedes and Megat Hamid at Chinese Academy of Medical Sciences Oxford Institute, University of Oxford. This has resulted in articles in two highly prestigious immunology journals, Science Immunology and Nature Immunology. Both papers elucidate mechanisms involved in T cell mediated tumour control and may represent novel avenues for immunotherapeutic cancer treatment.
Summaries of the findings:
Transmembrane domain-driven PD-1 dimers mediate T cell inhibition - Science Immunology
PD-1 is a potent immune checkpoint receptor on T cells which inhibits T cell activation upon engagement with its ligands PD-L1 and PD-L2, and it is a key target for checkpoint immunotherapy. PD-1 has thus far been considered monomeric, but in this paper, Kvalvaag and his collaborators in New York show that PD-1 and its ligands can dimerize in cis (in the plane of the plasma membrane) on the T cell surface through interactions within their transmembrane domains. Limiting PD-1 dimerization in cis weakens T cell inhibition upon ligand binding and enhances T cell mediated anti-tumour activity.
Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity - Nature Immunology
Expression of the integrin CD103 on tumor infiltrating CD8+ T cells is associated with better clinical prognosis in cancer patients. However, the molecular mechanisms behind CD103-mediated protection have remained elusive. In this paper, Kvalvaag and his collaborators in Oxford show that this is mediated by a transient interaction with another integrin, CD61, in T cell receptor microclusters at the immunological synapse. This interaction enhances cytotoxic T cell effector functions and acts as a marker for non-exhausted T cells.
Links:
Transmembrane domain-driven PD-1 dimers mediate T cell inhibition.
Philips EA, Liu J, Kvalvaag A, Mørch AM, Tocheva AS, Ng C, Liang H, Ahearn IM, Pan R, Luo CC, Leithner A, Qin Z, Zhou Y, Garcia-España A, Mor A, Littman DR, Dustin ML, Wang J, Kong XP.
Sci Immunol. 2024 Mar 8;9(93):eade6256. doi: 10.1126/sciimmunol.ade6256. Epub 2024 Mar 8.
PMID: 38457513
Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.
Hamid MHBA, Cespedes PF, Jin C, Chen JL, Gileadi U, Antoun E, Liang Z, Gao F, Teague R, Manoharan N, Maldonado-Perez D, Khalid-Alham N, Cerundolo L, Ciaoca R, Hester SS, Pinto-Fernández A, Draganov SD, Vendrell I, Liu G, Yao X, Kvalvaag A, Dominey-Foy DCC, Nanayakkara C, Kanellakis N, Chen YL, Waugh C, Clark SA, Clark K, Sopp P, Rahman NM, Verrill C, Kessler BM, Ogg G, Fernandes RA, Fisher R, Peng Y, Dustin ML, Dong T.
Nat Immunol. 2024 Apr 1. doi: 10.1038/s41590-024-01802-3. Online ahead of print.
PMID: 38561495
The Cellular membrane dynamics research group, headed by Harald A. Stenmark