Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Kumar A

PROVIDER: S-EPMC9250623 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Kumar Anupam A Mohamed Esraa E Tong Schuyler S Chen Katharine K Mukherjee Joydeep J Lim Yunita Y Wong Cynthia M CM Boosalis Zoe Z Shai Anny A Pieper Russell O RO Gupta Nalin N Perry Arie A Bollen Andrew W AW Molinaro Annette M AM Solomon David A DA Shieh Joseph T C JTC Phillips Joanna J JJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20220701 13

<h4>Purpose</h4>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.<h4>Experimental design</h4>We used multiplex immune-profiling, ...[more]

PMID: 35511927

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Dataset Information

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

Purpose

Experimental design

Results

Conclusions

Publications

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

Similar Datasets

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