Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation.

Autor: Wischnewski V; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Maas RR; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Aruffo PG; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Soukup K; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland., Galletti G; Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Milan, Italy., Kornete M; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland., Galland S; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Fournier N; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Translational Data Science, Swiss Institute of Bioinformatics, Lausanne, Switzerland., Lilja J; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland., Wirapati P; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland.; Translational Data Science, Swiss Institute of Bioinformatics, Lausanne, Switzerland., Lourenco J; Translational Data Science, Swiss Institute of Bioinformatics, Lausanne, Switzerland., Scarpa A; Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Milan, Italy., Daniel RT; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Hottinger AF; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Brouland JP; Department of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Losurdo A; Oncology Department, IRCCS Humanitas Research Hospital, Milan, Italy., Voulaz E; Department of Biomedical Sciences, Humanitas University, Milan, Italy.; Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Milan, Italy., Alloisio M; Department of Biomedical Sciences, Humanitas University, Milan, Italy.; Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Milan, Italy., Hegi ME; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Lugli E; Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Milan, Italy., Joyce JA; Department of Oncology, University of Lausanne, Lausanne, Switzerland. johanna.joyce@unil.ch.; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. johanna.joyce@unil.ch.; Agora Cancer Research Centre Lausanne, Lausanne, Switzerland. johanna.joyce@unil.ch.; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. johanna.joyce@unil.ch.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Jun; Vol. 4 (6), pp. 908-924. Date of Electronic Publication: 2023 May 22.
DOI: 10.1038/s43018-023-00566-3
Abstrakt: The immune-specialized environment of the healthy brain is tightly regulated to prevent excessive neuroinflammation. However, after cancer development, a tissue-specific conflict between brain-preserving immune suppression and tumor-directed immune activation may ensue. To interrogate potential roles of T cells in this process, we profiled these cells from individuals with primary or metastatic brain cancers via integrated analyses on the single-cell and bulk population levels. Our analysis revealed similarities and differences in T cell biology between individuals, with the most pronounced differences observed in a subgroup of individuals with brain metastasis, characterized by accumulation of CXCL13-expressing CD39 + potentially tumor-reactive T (pTRT) cells. In this subgroup, high pTRT cell abundance was comparable to that in primary lung cancer, whereas all other brain tumors had low levels, similar to primary breast cancer. These findings indicate that T cell-mediated tumor reactivity can occur in certain brain metastases and may inform stratification for treatment with immunotherapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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