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

• DOI: 10.1158/1078-0432.c.6531363.v1
• Publication Date: 2023-04-01T06:09:12Z
• Authors: 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
• Keywords: CXCL14

<div>AbstractPurpose:<p>The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As determinants glioma-associated immune are relatively poorly understood, study with more robust tumor-associated responses may be particularly useful identify novel immunomodulatory factors that can promote T-cell effector function glioma.</p>Experimental Design:<p>We used multiplex immune-profiling, proteomic profiling, and gene expression analysis define two molecular subtypes modulate this response. We then patient-derived cultures an immunocompetent murine model for malignant analyze ability tumor-intrinsic a CD8<sup>+</sup> response.</p>Results:<p>As compared isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers activated cytotoxic T cells Iba1<sup>+</sup> microglia/macrophages, MHC class I expression, enrichment genes associated antigen presentation processing, cell secretion chemokine CXCL14. CXCL14 promoted chemotaxis <i>in vitro</i>, recruited tumor-infiltrating vivo</i>, prolonged overall survival T-cell–dependent manner. The molecule B7-H3 was also highly expressed PXA.</p>Conclusions:<p>We lower grade astrocytoma PXA as having immune-rich suggest vulnerable immunotherapeutic modulation. important determinant microenvironment, sufficient antitumor response.</p></div>