FGL2172-220肽通过调节肿瘤微环境中的免疫抑制细胞,改善HCMV-IE1mut疫苗对胶质母细胞瘤的抗肿瘤效果。

IF 6.5 2区 医学 Q1 IMMUNOLOGY Oncoimmunology Pub Date : 2024-12-31 Epub Date: 2024-11-06 DOI:10.1080/2162402X.2024.2423983
Shan Wang, Shasha Jiang, Xu Li, Huan Huang, Xu Qiu, Meng Yu, Xiaoli Yang, Fengjun Liu, Chen Wang, Wen Shen, Yunyang Wang, Bin Wang
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引用次数: 0

摘要

多形性胶质母细胞瘤(GBM)是一种侵袭性极强的原发性脑肿瘤,其特点是预后不良且缺乏有效的治疗方法。近年来,利用基于肿瘤特异性或肿瘤相关抗原的序列来激活针对肿瘤细胞的免疫反应的多肽疫苗已成为一种新的治疗策略。在这项研究中,我们针对肿瘤相关抗原纤维蛋白原样蛋白 2(FGL2)开发了一种新型治疗性多肽疫苗,其主要表位肽通过连接子串联到 HCMV-IE1mut 的 C 端。我们利用这种疫苗比较了单独使用 HCMV-IE1mut 与使用 HCMV-IE1mut-FGL2172-220 的疗效,并研究了 HCMV-IE1mut-FGL2172-220 治疗胶质瘤的潜在作用机制。为了确定疫苗的疗效,我们使用了一种原位 GBM 模型(GL261-IE1-luc 细胞)。用HCMV-IE1mut-FGL2172-220治疗可产生抗肿瘤效果并延长GL261动物模型的存活时间。我们通过免疫荧光观察到肿瘤微环境(TME)中小胶质细胞、调节性T细胞(Treg)和髓源抑制细胞(MDSC)的比例降低。流式细胞术显示,与单独使用HCMV-IE1mut相比,使用HCMV-IE1mut-FGL2172-220可增加CD8+ T细胞和组织驻留记忆T细胞(TRM)的比例。ELISA 分析表明,它能提高这些细胞分泌肿瘤特异性 IFN-γ 和 TNF-α,并下调 IL-6 和 IL-10 的表达。我们的研究表明,长肽FGL2172-220提高了HCMV-IE1mut的抗肿瘤疗效,可能是通过重塑胶质瘤微环境中的免疫细胞。这些发现为开发治疗性抗原肽疫苗以提高抗肿瘤效果奠定了基础。
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FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.

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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
期刊最新文献
FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment. HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer. Markers of tumor-associated macrophages and microglia exhibit high intratumoral heterogeneity in human glioblastoma tissue. Estrogen-related differences in antitumor immunity and gut microbiome contribute to sexual dimorphism of colorectal cancer. Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis.
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