{"doi":"10.1158/1078-0432.c.6531363","title":"Data from CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma","abstract":"<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>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<sup>+</sup> T-cell response.</p>Results:<p>As compared with isocitrate dehydrogenase (IDH)-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8<sup>+</sup> T cells and Iba1<sup>+</sup> 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<sup>+</sup> T-cell chemotaxis <i>in vitro</i>, recruited tumor-infiltrating CD8<sup>+</sup> T cells <i>in vivo</i>, and prolonged overall survival in a cytotoxic T-cell–dependent manner. The immunomodulatory molecule B7-H3 was also highly expressed in PXA.</p>Conclusions:<p>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<sup>+</sup> T-cell response.</p></div>","journal":null,"year":2023,"id":405687,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407753,"name":"Esraa Mohamed","orcid":"0000-0002-6677-5103","position":1,"is_corresponding":false},{"id":858381,"name":"Schuyler Tong","orcid":null,"position":2,"is_corresponding":false},{"id":846483,"name":"Katharine Chen","orcid":"0000-0001-6698-1217","position":3,"is_corresponding":false},{"id":1175074,"name":"Joydeep Mukherjee","orcid":"0009-0004-6180-7905","position":4,"is_corresponding":false},{"id":854062,"name":"Yunita Lim","orcid":null,"position":5,"is_corresponding":false},{"id":1175075,"name":"Cynthia Wong","orcid":"0000-0002-8939-0468","position":6,"is_corresponding":false},{"id":710642,"name":"Zoe Boosalis","orcid":null,"position":7,"is_corresponding":false},{"id":523425,"name":"Anny Shai","orcid":"0000-0001-7231-9326","position":8,"is_corresponding":false},{"id":474447,"name":"Russell O. Pieper","orcid":null,"position":9,"is_corresponding":false},{"id":250771,"name":"Nalin Gupta","orcid":"0000-0001-9539-7052","position":10,"is_corresponding":false},{"id":226438,"name":"Arie Perry","orcid":"0000-0002-8300-7261","position":11,"is_corresponding":false},{"id":267675,"name":"Andrew W. Bollen","orcid":"0000-0001-9852-5224","position":12,"is_corresponding":false},{"id":238091,"name":"Annette M. Molinaro","orcid":"0000-0002-9854-7404","position":13,"is_corresponding":false},{"id":236611,"name":"David A. Solomon","orcid":"0000-0003-4571-7999","position":14,"is_corresponding":false},{"id":239233,"name":"Joseph T.C. Shieh","orcid":null,"position":15,"is_corresponding":false},{"id":87614,"name":"Joanna J. Phillips","orcid":"0000-0002-3789-8120","position":16,"is_corresponding":false},{"id":1175073,"name":"Anupam Kumar","orcid":"0000-0002-6608-3860","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:20:54.430249Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}