黑色素瘤作为一种高度恶性的皮肤癌，在肿瘤治疗研究中备受关注。现在，肿瘤免疫治疗，特别是免疫治疗与其他治疗的联合使用，越来越受到关注。吲哚胺2,3-二氧化酶2（IDO2）是一种限速酶，在免疫抑制犬尿液中的色氨酸代谢途径中高表达于黑色素瘤组织中。此外，IDO2显著抑制体内的抗肿瘤免疫，并成为黑色素瘤治疗的一种新靶标。福乐沙它唑作为一种肠道抗菌剂，被发现可以抑制Stat3的表达，发挥抗肿瘤作用。因此，本研究旨在检验通过弱化沙门氏菌输送自行设计的IDO2-小干扰RNA（siRNA）和福乐沙它唑治疗黑色素瘤负载小鼠的疗效及其潜在的机制。 在体外，流式细胞术、CCK-8和集落形成能力实验分别检测了福乐沙它唑对黑色素瘤的作用。构建了siRNA-IDO2的质粒，并建立了携带黑色素瘤的小鼠模型。治疗后，监测肿瘤生长和存活率，通过HE染色检测肿瘤组织的形态学改变。通过Western blotting检测相关蛋白的表达，通过IHC和IF检测肿瘤组织中CD4和CD8阳性T细胞的表达情况，并通过流式细胞术检测脾脏中CD4和CD8阳性T细胞的比例。 结果表明，联合治疗有效地抑制了黑色素瘤细胞中Stat3的磷酸化和IDO2的表达水平，从而有效地抑制了肿瘤生长并延长了肿瘤负载小鼠的生存时间。机制研究揭示，与对照组和单药治疗组相比，联合治疗组减轻了肿瘤细胞异型性，增加了凋亡率，增强了T淋巴细胞在肿瘤组织中的浸润，并增加了脾脏中的CD4+和CD8+ T淋巴细胞，表明机制可能与抑制肿瘤细胞增殖、增加凋亡和增强细胞免疫有关。 总之，IDO2-siRNA联合福乐沙它唑治疗对于黑色素瘤负载小鼠的治疗具有重要作用，能增强肿瘤免疫力，并为临床治疗黑色素瘤寻找新的联合方法提供实验依据。 版权所有© Bentham Science Publishers；如有疑问，请发送电子邮件至epub@benthamscience.net。

Melanoma, as a highly malignant skin cancer, is a hot topic in oncology treatment research. Nowadays, tumor immunotherapy, especially immunotherapy combined with other therapies, has attracted more and more attention. Indoleamine 2,3-dioxygenase 2 (IDO2), a rate limiting enzyme of the tryptophan metabolism pathway in the urine of dogs with immunosuppression, is highly expressed in melanoma tissue. Additionally, IDO2 significantly inhibits the anti-tumor immunity of the body and has become a novel target of melanoma treatment. Nifuroxazide, as an intestinal antibacterial agent, was found to be able to inhibit Stat3 expression and exert anti-tumor effect. Therefore, the present study aimed to examine the therapeutic effect of a self-designed IDO2-small interfering RNA (siRNA) delivered by attenuated Salmonella combined with nifuroxazide on melanoma-bearing mice, as well as determined its underlying mechanism.The effect of nifuroxazide on melanoma was detected by flow cytometry, CCK-8 and colony forming ability assays respectively in vitro. The plasmid of siRNA-IDO2 was constructed, and the mice bearing melanoma model was established. After the treatment, the tumor growth and survival rate were monitored, and the morphological changes of tumor tissue were detected by HE staining. The expression of related proteins was detected by Western blotting, and the expression of CD4 and CD8 positive T cells in tumor tissue was detected by IHC and IF, and the proportion of CD4 and CD8 positive T cells in spleen was detected by flow cytometry.The results demonstrated that the combination therapy effectively inhibited the phosphorylation of Stat3 and the expression level of IDO2 in melanoma cells, which effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. The mechanistic study revealed that, compared with control groups and monotherapy groups, the combination treatment group reduced the atypia of tumor cells, increased the apoptotic rate, enhanced the infiltration of T lymphocytes in tumor tissue and increased the CD4+ and CD8+ T lymphocytes in the spleen, suggesting that the mechanism may be associated with the inhibition of tumor cell proliferation, the increase of apoptosis and the enhancement of the cellular immunity.In conclusion, IDO2-siRNA combined with nifuroxazide therapy could serve a significant role in the treatment of melanoma-bearing mice, enhance the tumor immunity and provide an experimental basis for identifying a novel combination method for the treatment of melanoma clinically.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.