针对肿瘤微环境髓系抑制细胞的新型ImC疫苗抗肿瘤作用及免疫机制研究

Tumor microenvironment is closely related to the occurrence, development and metastasis of tumor. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironments play an important role in the process. Previous studies have shown that MDSCs were a group of heterogeneity immature myeloid cells (ImCs), which suppressed immune activity through a variety of mechanisms. MDSCs can lead to the "immune escape" of tumors and promote tumor growth and metastasis. Therefore, we designed and prepared a novel ImC vaccine against MDSCs. The ImC vaccine could suppress or eliminate MDSCs in the tumor microenvironments and promote the cellular and humoral immunity to achieve the purpose of anti-tumor. Our preliminary studies indicated that the ImC vaccine showed great anti-tumor activity in both tumor prevention and tumor treatment, however, the immune mechanisms of the ImC vaccine remains unclear. This study will mainly focus on the effects of the ImC vaccine on tumor microenvironments and finding the effector cells and molecules, which will clarify the immunomodulatory mechanisms of the ImC vaccine. This study will reveal the immunomodulatory mechanism of the ImC vaccine, which will provide new ideas and a new perspective for immunotherapy and also provide a new choice for the clinical treatment of cancer.

肿瘤的发生、发展和转移与肿瘤微环境密切相关, 肿瘤微环境中的髓系抑制性细胞（Myeloid-derived suppressor cells, MDSCs）在这一过程中扮演了重要角色。研究表明，MDSCs是一群异质性的不成熟髓样细胞（Immature myeloid cells, ImCs)，可通过多种机制帮助肿瘤细胞实现"免疫逃逸"并促进肿瘤生长和转移。因此，针对该细胞群，我们设计并制备了一种全新的ImC疫苗，拟采用免疫疗法，通过清除或抑制肿瘤微环境中MDSCs，促进机体细胞免疫和体液免疫，达到抗肿瘤目的。前期结果显示，ImC疫苗对肿瘤预防和治疗均有良好效果，但其免疫机制仍不清楚。本项目将重点研究该疫苗对肿瘤微环境的影响，寻找其效应细胞和效应分子，阐明其免疫调节机制。本项目的实施有助于揭示新型ImC疫苗的免疫调节机制，为肿瘤免疫治疗提供新思路和新视角，也为临床癌症治疗提供新选择。

肿瘤的发生、发展和转移与肿瘤微环境密切相关。肿瘤微环境中的髓系抑制性细胞（Myeloid-derived suppressor cells, MDSCs）在这一过程中扮演了重要角色。MDSCs是一群异质性的不成熟髓样细胞（Immature myeloid cells, ImCs），可通过多种机制帮助肿瘤细胞实现“免疫逃逸”并促进肿瘤生长和转移。因此，我们针对该细胞群设计并制备了一种全新的ImC疫苗，拟采用免疫疗法，通过清除或抑制肿瘤微环境中MDSCs，促进机体细胞免疫和体液免疫，达到抗肿瘤目的。前期结果显示，ImC疫苗对肿瘤预防和治疗均有良好效果，但其免疫机制仍不清楚。本项目将重点研究该疫苗对肿瘤微环境的影响，寻找其效应细胞和效应分子，阐明其免疫调节机制。本项目进展较为顺利，已经完成了ImC疫苗的制备和鉴定，4T1皮下移植瘤、CT26皮下移植瘤和CT26肺转移瘤三种肿瘤模型的预防性免疫疗效评价，4T1皮下移植瘤、CT26皮下移植瘤和LL/2皮下移植瘤三种肿瘤模型的治疗性性免疫疗效评价，并通过CT26皮下移植瘤模型研究ImC疫苗的免疫持久性、对机体体液免疫和细胞免疫的作用和对肿瘤微环境中多种免疫细胞的影响，最后对ImC疫苗的体内安全性进行了初步评估。结果显示，采用ImC疫苗进行预防性免疫和治疗性免疫在多种肿瘤模型中显示出良好疗效，具有较好的免疫持久性；ImC疫苗可以通过降低肿瘤微环境中MDSCs等免疫抑制性细胞数量，并促进机体体液免疫和细胞免疫达到良好地治疗效果；同时，未发现ImC疫苗有明显的毒副作用。