E2F转录因子是公认的致癌分子，并且最近有研究报告了它们与免疫细胞浸润的相关性。本研究探讨了E2F转录因子3(E2F3)在鼻咽癌(NPC)的生长和肿瘤微环境(TME)中的影响和机制。通过丰富的生物信息学分析筛选出NPC中异常表达的转录因子。通过反转录定量聚合酶链反应和Western blot分析分析NPC细胞中的基因表达。通过细胞计数套件-8、5-乙炔基-2'-脱氧尿嘧啶标记、Transwell试验和异种移植瘤模型分析NPC细胞的恶性行为。TPA诱导的THP-1细胞(巨噬细胞)在NPC细胞的条件培养基中培养，以模拟体内的肿瘤相关巨噬细胞(TAMs)，并将这些TAMs与CD8+ T细胞共培养。通过染色质免疫共沉淀和荧光素酶报告基因分析验证了E2F3对细胞分裂蛋白调节因子1(PRC1)和含有蝴蝶病毒IAP重复结构蛋白的第5号(BIRC5)的调节作用。E2F3在NPC细胞中高表达，其敲低抑制了细胞的恶性行为和肿瘤形成能力。E2F3敲低条件下，TAMs中M2细胞因子CD163和白介素-10表达下调，进一步促进了共培养的CD8+ T细胞的增殖和活化。E2F3促进了PRC1和BIRC5的转录。此外，NPC细胞中的PRC1或BIRC5上调恢复了NPC细胞的恶性特性，使TAMs向M2表型重编程，并抑制了CD8+ T细胞的增殖和活化。本研究表明，E2F3通过激活PRC1和BIRC5在NPC中形成免疫抑制型TME。抑制参与其中的任何成员都可能有利于肿瘤的消除。©2023作者。由John Wiley & Sons Ltd.出版的免疫、炎症和疾病。

E2F transcription factors are well-recognized oncogenic molecules, and their correlation with immune cell infiltration has recently been reported. This work studies the impacts and mechanism of E2F transcription factor 3 (E2F3) in the growth and tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC).Aberrantly expressed transcription factors in NPC were screened by abundant bioinformatics analyses. Gene expression in NPC cells was analyzed by reverse transcription-quantitative polymerase chain reaction and Western blot analyses. Malignant behaviors of NPC cells were analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine labeling, Transwell assays, and xenograft tumor models. TPA-induced THP-1 cells (macrophages) were cultured in the conditioned medium of NPC cells to mimic tumor-associated macrophages (TAMs) in vivo, and these TAMs were cocultured with CD8+ T cells. Regulation of E2F3 on protein regulator of cytokinesis 1 (PRC1) and baculoviral IAP repeat containing 5 (BIRC5) was validated by chromatin immunoprecipitation and luciferase reporter assays.E2F3 was highly expressed in NPC cells, and its knockdown suppressed malignant behavior and tumorigenic ability of the cells. The E2F3 knockdown condition downregulated M2 cytokines CD163 and interleukin-10 in TAMs, which further enhanced proliferation and activation of the cocultured CD8+ T cells. E2F3 promoted transcription of PRC1 and BRIC5. Furthermore, PRC1 or BRIC5 upregulation in NPC cells restored the malignant properties of NPC cells, reprogrammed the TAMs to M2 phenotype, and suppressed the CD8+ T cell proliferation and activation.This work suggests that E2F3 renders an immunosuppressive TME in NPC by activating PRC1 and BIRC5. Suppression of any member involved might favor tumor elimination.© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.