{"doi":"10.3390/cancers16152629","title":"VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma","abstract":"Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor–cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA’s binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA–VSIG axis to enhance anti-tumor responses.","journal":"Cancers","year":2024,"id":445137,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1261530,"name":"Juliana M. Pensabene","orcid":null,"position":1,"is_corresponding":false},{"id":584348,"name":"Phillip M. Galbo","orcid":"0000-0002-5391-598X","position":2,"is_corresponding":false},{"id":511974,"name":"Negar Sadeghipour","orcid":"0000-0002-6348-4490","position":3,"is_corresponding":false},{"id":254337,"name":"Joanne Xiu","orcid":"0000-0001-8744-5827","position":4,"is_corresponding":false},{"id":1261531,"name":"Kirsten Moziak","orcid":null,"position":5,"is_corresponding":false},{"id":420465,"name":"Rita M. Yazejian","orcid":"0009-0003-3700-9025","position":6,"is_corresponding":false},{"id":435776,"name":"Rachel L. Welch","orcid":"0000-0003-4698-2372","position":7,"is_corresponding":false},{"id":1261532,"name":"W. Robert Bell","orcid":null,"position":8,"is_corresponding":false},{"id":458977,"name":"Soma Sengupta","orcid":"0000-0003-4577-1397","position":9,"is_corresponding":false},{"id":1186993,"name":"Sonikpreet Aulakh","orcid":"0000-0001-7150-5805","position":10,"is_corresponding":false},{"id":232275,"name":"Charles G. Eberhart","orcid":"0000-0002-2910-9427","position":11,"is_corresponding":false},{"id":329713,"name":"David M. Loeb","orcid":"0000-0002-7319-5000","position":12,"is_corresponding":false},{"id":333806,"name":"Emad N. 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