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Genes (Basel) ; 15(5)2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790160

RESUMO

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.


Assuntos
Tumores Neuroendócrinos , Neoplasias Hipofisárias , Transcriptoma , Microambiente Tumoral , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/imunologia , Neoplasias Hipofisárias/patologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/patologia , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica/métodos , Masculino , Feminino , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade , Adulto
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