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Immunol."],"abstract":"<jats:p>Epstein\u2013Barr Virus (EBV) is a tumor associated virus that modulates not only the infected cells but also innate and adaptive immunity. Macrophages play a key role in tumor development and progression. Particularly, the M2 phenotype (CD163) with anti-inflammatory activity contributes to a favorable microenvironment for tumor development while the M1 (CD68) proinflammatory phenotype contributes to a restrictive one. In the context of pediatric EBV infection, little is known about macrophage contribution to PD-L1 expression, a molecule involved in immune exhaustion. We studied tonsils of primary infected (PI), healthy carriers (HC), reactivated (R), and not infected (NI) pediatric patients. Positive correlations were demonstrated for CD68+PD-L1+ in R and for CD163+PD-L1+ only in PI. Furthermore, CD163+PD-L1+ cell numbers were higher than PD-L1+CD68+ in PI patients. In addition, a positive correlation between PD-L1+CD163+ cells and LMP1 viral latent protein was observed in PI patients, and a positive correlation between PD-L1+CD68+ cells and BMRF1 lytic antigen was demonstrated. A positive correlation between TGF-\u03b2 and PD-L1 expression was demonstrated in HC patients. Our findings indicate that EBV\u2019s lytic and latent antigens might be regulating macrophages\u2019 PD-L1 expression, particularly in PI patients, whereas, surprisingly, only TGF-\u03b2 could be related to total PD-L1 upregulation. Given the relevance of macrophages and the PD-1\/PD-L1 pathway in tumor progression and survival, more studies in early EBV infection could help to develop EBV-associated tumor therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2022.940910","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:30:56Z","timestamp":1668400256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["PD-L1 is upregulated in CD163+ tonsillar macrophages from children undergoing EBV primary infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Agustina","family":"Moyano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Ferressini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"De 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