Regulatory T cell depletion promotes myeloid cell activation and glioblastoma response to anti-PD1 and tumor-targeting antibodies
Year: 2025
Type: article
Abstract: Glioblastoma is invariably lethal and responds poorly to immune checkpoint blockade. Here, we examined the impact of regulatory T (Treg) cell depletion on glioblastoma progression and immunotherapy responsiveness. In human glioblastoma, elevated Treg cell signatures correlated with poorer survival outcomes, with these cells expressing high levels of CD25. In Nf1 −/− Pten −/− EGFRvIII + glioblastoma-bearing mice, a single dose of non-interleukin-2 (IL-2) blocking (NIB) anti-CD25 (anti-CD25 NIB ) antibody depleted Treg cells and promoted CD8 + T cell clonal expansion and partial tumor control, further enhanced by programmed cell death-1 (PD1)-blockade. Treg cell depletion induced interferon-γ (IFN-γ)-dependent tumor microenvironment remodeling, increasing Fcγ receptor (FcγR) expression on intratumoral myeloid cells and enhancing phagocytosis. Combination of anti-CD25 NIB with anti-EGFRvIII tumor-targeting antibodies resulted in complete tumor control. Anti-human CD25 NIB treatment of glioblastoma patient-derived tumor fragments effectively depleted Treg cells and activated CD8 + T cells. These findings underscore the therapeutic relevance of Treg targeting in glioblastoma and unveil potent combination strategies for anti-CD25 NIB based on innate cell activation.
Source: Immunity
Authors: Felipe Galvez-Cancino, Mariela Navarrete, Gordon Beattie, Simone Puccio, Enrique Conde-Gallastegi, Kane Foster, Yasmin Morris, Teerapon Sahwangarrom, Despoina Karagianni, Jiali Liu, Alvin J.X. Lee, Dimitrios A. Garyfallos, Alexander P. Simpson, Gerasimos-Theodoros Mastrokalos, Francesco Nannini, Cristobal Costoya, Varshaa Anantharam, Beatrice Claudia Cianciotti, Leanne Bradley, Claudia Garcia-Diaz, Melanie Clements, Aditya Shroff, Fatemeh Vahid Dastjerdi, Enrique Miranda Rota, Shahida Sheraz, Robert Bentham, Imran Uddin, Henning Walczak, Alvaro Lladser, James L. Reading, Kerry A. Chester, Martin A. Pule, Paul M. Brennan, Samuel Marguerat, Simona Parrinello, Karl S. Peggs, Nicholas McGranahan, Enrico Lugli, Kevin Litchfield, Steven M. Pollard, Sergio A. Quezada
Institutions: University of Oxford, University College London, Cancer Research UK, Institute of Genetic and Biomedical Research, National Research Council, IRCCS Humanitas Research Hospital, Edinburgh Cancer Research, MRC Centre for Regenerative Medicine, University of Edinburgh, University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, San Sebastián University, Fundación Ciencia and Vida
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Fondazione AIRC per la ricerca sul cancro ETS, Cancer Research Institute, Cancer Research UK, National Institute for Health and Care Research, Associazione Italiana per la Ricerca sul Cancro, Fondazione Italiana per la Ricerca sul Cancro, Université Catholique de Louvain, Fondo Nacional de Desarrollo Científico y Tecnológico
OpenAlex ID: W4409737148