American Association for Cancer Research
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Supplementary Figure from CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma

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journal contribution
posted on 2023-03-31, 23:15 authored by Anupam Kumar, Esraa Mohamed, Schuyler Tong, Katharine Chen, Joydeep Mukherjee, Yunita Lim, Cynthia M. Wong, Zoe Boosalis, Anny Shai, Russell O. Pieper, Nalin Gupta, Arie Perry, Andrew W. Bollen, Annette M. Molinaro, David A. Solomon, Joseph T.C. Shieh, Joanna J. Phillips
Supplementary Figure from CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma




UCSF Helen Diller Family Comprehensive Cancer Center Laboratory for Cell Analysis



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. 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. 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. 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.

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