越来越多的证据表明肠道真菌失调在结直肠癌（CRC）的发生和进展中起着至关重要的作用。据报道，肠道真菌通过调节肿瘤免疫而加剧结直肠癌的严重程度。我们前期的研究表明，机会性致病真菌热带假丝酵母（C.tropicalis）通过增强MDSCs的免疫抑制功能、激活MDSCs的NLRP3炎症小体来促进CRC进展。然而，CRC中NLRP3炎症小体激活产生的IL-1β与热带念珠菌增强MDSCs免疫抑制功能之间的关系尚不清楚。利用TCGA数据库分析IL-1β与MDSCs免疫抑制功能相关基因的关系在人类结直肠癌中。免疫荧光染色检测人结直肠癌组织中IL-1β的表达。对热带念珠菌刺激的 MDSC 的培养上清液进行蛋白质组分析。进行了补充和阻断IL-1β以及抑制NLRP3炎症小体激活的实验。利用MC38结肠癌细胞系建立小鼠结肠癌异种移植模型。对CRC临床样本的分析表明，IL-1β的高表达与肿瘤浸润的MDSCs的免疫抑制功能密切相关。体外实验结果表明，热带念珠菌刺激的MDSCs分泌最多的细胞因子是IL-1β。体外补充IL-1β进一步增强热带念珠菌刺激的MDSCs的免疫抑制功能，并且NLRP3-IL-1β轴介导热带念珠菌增强的MDSCs的免疫抑制功能。最后，阻断 MDSC 分泌的 IL-1β 增强了抗肿瘤免疫力并减轻了热带念珠菌相关的结肠癌。热带菌通过 NLRP3 炎性体促进 MDSC 过度分泌 IL-1β。 IL-1β进一步增强MDSCs的免疫抑制功能，抑制抗肿瘤免疫，从而促进CRC的进展。因此，针对 MDSC 分泌的 IL-1β 可能是治疗 CRC 的潜在免疫治疗策略。© 2024。作者。

There is increasing evidence that gut fungi dysbiosis plays a crucial role in the development and progression of colorectal cancer (CRC). It has been reported that gut fungi exacerbate the severity of CRC by regulating tumor immunity. Our previous studies have shown that the opportunistic pathogenic fungal pathogen, Candida tropicalis (C. tropicalis) promotes CRC progression by enhancing the immunosuppressive function of MDSCs and activating the NLRP3 inflammasome of MDSCs. However, the relationship between IL-1β produced by NLRP3 inflammasome activation and the immunosuppressive function of MDSCs enhanced by C. tropicalis in CRC remains unclear.The TCGA database was used to analyze the relationship between IL-1β and genes related to immunosuppressive function of MDSCs in human CRC. The expression of IL-1β in human CRC tissues was detected by immunofluorescence staining. The proteomic analysis was performed on the culture supernatant of C. tropicalis-stimulated MDSCs. The experiments of supplementing and blocking IL-1β as well as inhibiting the NLRP3 inflammasome activation were conducted. A mouse colon cancer xenograft model was established by using MC38 colon cancer cell line.Analysis of CRC clinical samples showed that the high expression of IL-1β was closely related to the immunosuppressive function of tumor-infiltrated MDSCs. The results of in vitro experiments revealed that IL-1β was the most secreted cytokine of MDSCs stimulated by C. tropicalis. In vitro supplementation of IL-1β further enhanced the immunosuppressive function of C. tropicalis-stimulated MDSCs and NLRP3-IL-1β axis mediated the immunosuppressive function of MDSCs enhanced by C. tropicalis. Finally, blockade of IL-1β secreted by MDSCs augmented antitumor immunity and mitigated C. tropicalis-associated colon cancer.C. tropicalis promotes excessive secretion of IL-1β from MDSCs via the NLRP3 inflammasome. IL-1β further enhances the immunosuppressive function of MDSCs to inhibit antitumor immunity, thus promoting the progression of CRC. Therefore, targeting IL-1β secreted by MDSCs may be a potential immunotherapeutic strategy for the treatment of CRC.© 2024. The Author(s).