Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Ciudad de México 06720, Mexico.
Laboratorio Nacional de Vacunología y Virus Tropicales, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11350, Mexico.
Genes (Basel). 2024 Apr 24;15(5):531. doi: 10.3390/genes15050531.
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 , , , , and were upregulated in all PitNETS, whereas , , and characterize the , -, and -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 , and as well as macrophage tumor infiltration could identify patients who can potentially benefit from treatment with immune checkpoint inhibitors.
垂体神经内分泌肿瘤（PitNET）已知被不同的免疫细胞浸润。尽管如此，它们在垂体肿瘤发生中的作用才刚刚开始被揭示。免疫微环境可以决定肿瘤的生物学和临床行为，并可能具有预后意义。为了评估 42 例不同谱系的 PitNET 中与免疫相关的基因表达，并将这种表达与浸润免疫细胞的存在相关联，我们进行了全转录组分析和 RT-qPCR。去卷积分析用于推断每个肿瘤中存在的免疫细胞类型，并通过免疫荧光确认免疫细胞的存在。我们发现了每个肿瘤谱系中具有特征性的免疫相关基因表达谱，包括编码白细胞介素和趋化因子的基因。、、、和在所有 PitNET 中均上调，而、和分别特征化为、-和-衍生的肿瘤。转录组去卷积分析表明，M2 巨噬细胞、CD4+T 细胞、CD8+T 细胞、NK 细胞和中性粒细胞可能浸润 PitNET。此外，通过免疫荧光验证了 CD4+和 CD8+T 细胞以及 NK 细胞的浸润。表达、和巨噬细胞肿瘤浸润可以识别出可能受益于免疫检查点抑制剂治疗的患者。
