{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:52:26Z","timestamp":1789537946608,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["R-2019-785-052"],"award-info":[{"award-number":["R-2019-785-052"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pituitary neuroendocrine tumors (PitNET) are known to be variably infiltrated by different immune cells. Nonetheless, their role in pituitary oncogenesis has only begun to be unveiled. The immune microenvironment could determine the biological and clinical behavior of a neoplasm and may have prognostic implications. To evaluate the expression of immune-related genes and to correlate such expression with the presence of infiltrating immune cells in forty-two PitNETs of different lineages, we performed whole transcriptome analysis and RT-qPCR. Deconvolution analysis was carried out to infer the immune cell types present in each tumor and the presence of immune cells was confirmed by immunofluorescence. We found characteristic expression profiles of immune-related genes including those encoding interleukins and chemokines for each tumor lineage. Genes such as IL4-I1, IL-36A, TIRAP, IL-17REL, and CCL5 were upregulated in all PitNETS, whereas IL34, IL20RA, and IL-2RB characterize the NR5A1-, TBX19-, and POU1F1-derived tumors, respectively. Transcriptome deconvolution analysis showed that M2 macrophages, CD4+ T cells, CD8+ T cells, NK cells, and neutrophils can potentially infiltrate PitNET. Furthermore, CD4+ and CD8+ T cells and NK cells infiltration was validated by immunofluorescence. Expression of CCL18, IL-5RA, and HLA-B as well as macrophage tumor infiltration could identify patients who can potentially benefit from treatment with immune checkpoint inhibitors.<\/jats:p>","DOI":"10.3390\/genes15050531","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T03:56:31Z","timestamp":1713930991000},"page":"531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Immune Microenvironment Landscape of Pituitary NeuroEndocrine Tumors, a Transcriptomic Approach"],"prefix":"10.3390","volume":"15","author":[{"given":"Sandra","family":"Vela-Pati\u00f1o","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Endocrinas, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"},{"name":"Laboratorio Nacional de Vacunolog\u00eda y Virus Tropicales, Departamento de Microbiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11350, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-8462","authenticated-orcid":false,"given":"Ma. Isabel","family":"Salazar","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Vacunolog\u00eda y Virus Tropicales, Departamento de Microbiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11350, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Taniguchi-Ponciano","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Endocrinas, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Vadillo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Oncol\u00f3gicas, Hospital de Oncolog\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Gomez-Apo","sequence":"additional","affiliation":[{"name":"\u00c1rea de Neuropatolog\u00eda, Servicio de Anatom\u00eda Patol\u00f3gica, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurea","family":"Escobar-Espa\u00f1a","sequence":"additional","affiliation":[{"name":"\u00c1rea de Neuropatolog\u00eda, Servicio de Anatom\u00eda Patol\u00f3gica, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-8800","authenticated-orcid":false,"given":"Vadim","family":"Perez-Koldenkova","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Microscopia Avanzada, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bonifaz","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunoqu\u00edmica, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"},{"name":"Coordinaci\u00f3n de Investigaci\u00f3n en Salud, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Aguilar-Flores","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-6654","authenticated-orcid":false,"given":"Daniel","family":"Marrero-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Endocrinas, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moises","family":"Mercado","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Endocrinas, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Ciudad de M\u00e9xico 06720, Mexico"},{"name":"Centro de Cancer, Hospital American British Cowdray, Sur 136 116, Las Am\u00e9ricas, \u00c1lvaro Obreg\u00f3n, Ciudad de M\u00e9xico 01120, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s12022-022-09703-7","article-title":"Overview of the 2022 WHO Classification of Pituitary Tumors","volume":"33","author":"Asa","year":"2022","journal-title":"Endocr. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1101\/gad.314617.118","article-title":"Roles of the immune system in cancer: From tumor initiation to metastatic progression","volume":"32","author":"Gonzalez","year":"2018","journal-title":"Genes. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1507\/endocrj.45.357","article-title":"Prevalence of lymphocytic infiltrate in 1400 pituitary adenomas","volume":"45","author":"Heshmati","year":"1998","journal-title":"Endocr. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1210\/jc.2009-1583","article-title":"Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma","volume":"95","author":"Lupi","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s12022-015-9383-6","article-title":"Immune Cell Infiltrates in Pituitary Adenomas: More Macrophages in Larger Adenomas and More T Cells in Growth Hormone Adenomas","volume":"26","author":"Lu","year":"2015","journal-title":"Endocr. 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