CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma.

Autor:	Kumar A; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Mohamed E; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Tong S; Department of Hematology Oncology, UCSF Benioff Children's Hospital - Oakland, University of California San Francisco, Oakland, California., Chen K; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Mukherjee J; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Lim Y; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Wong CM; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Boosalis Z; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Shai A; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Pieper RO; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Gupta N; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Perry A; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California.; Division of Neuropathology, Departments of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, California., Bollen AW; Division of Neuropathology, Departments of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, California., Molinaro AM; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California., Solomon DA; Division of Neuropathology, Departments of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, California., Shieh JTC; Division of Medical Genetics, Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, California.; Institute for Human Genetics, University of California San Francisco, San Francisco, California., Phillips JJ; Brain Tumor Center, Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California.; Division of Neuropathology, Departments of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, California.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Jul 01; Vol. 28 (13), pp. 2898-2910.
DOI:	10.1158/1078-0432.CCR-21-2830
Abstrakt:	Purpose: The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T-cell effector function in glioma. Experimental Design: We used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response. We then used patient-derived glioma cultures and an immunocompetent murine model for malignant glioma to analyze the ability of tumor-intrinsic factors to promote a CD8+ T-cell response. Results: As compared with isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages, increased MHC class I expression, enrichment of genes associated with antigen presentation and processing, and increased tumor cell secretion of the chemokine CXCL14. CXCL14 promoted activated CD8+ T-cell chemotaxis in vitro, recruited tumor-infiltrating CD8+ T cells in vivo, and prolonged overall survival in a cytotoxic T-cell-dependent manner. The immunomodulatory molecule B7-H3 was also highly expressed in PXA. Conclusions: We identify the MAPK-activated lower grade astrocytoma PXA as having an immune-rich tumor microenvironment and suggest this tumor may be particularly vulnerable to immunotherapeutic modulation. We also identify CXCL14 as an important determinant of the glioma-associated immune microenvironment, sufficient to promote an antitumor CD8+ T-cell response. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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