CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme.
The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme.
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高比例的恶性胶质瘤被人巨细胞病毒(HCMV)感染,在这些肿瘤中发现HCMV基因及其产物的内源性表达。HCMV抗原表达及其在胶质瘤发生中的意义已成为多形性胶质母细胞瘤(GB)患者过继性细胞免疫治疗(ACT)策略的一个有前景的靶点。由于肿瘤微环境中的抗原特异性T细胞因胶质母细胞瘤的免疫抑制性质而缺乏有效的抗肿瘤免疫应答,CMV特异性ACT依赖于利用免疫优势HCMV抗原在体外扩增CMV特异性CD8+ T细胞。鉴于仍有若干障碍有待克服,近期临床试验已勾勒出在肿瘤复发前进行CMV特异性ACT的可行性,其不良反应极小,且中位总生存期和无进展生存期均有显著改善。本综述讨论了HCMV在胶质瘤发生、疾病预后中的作用,以及在GB肿瘤微环境中利用HCMV诱导的免疫原性来开发有效CMV特异性ACT的最新突破。
A high percentage of malignant gliomas are infected by human cytomegalovirus (HCMV), and the endogenous expression of HCMV genes and their products are found in these tumors. HCMV antigen expression and its implications in gliomagenesis have emerged as a promising target for adoptive cellular immunotherapy (ACT) strategies in glioblastoma multiforme (GB) patients. Since antigen-specific T cells in the tumor microenvironments lack efficient anti-tumor immune response due to the immunosuppressive nature of glioblastoma, CMV-specific ACT relies on in vitro expansion of CMV-specific CD8 + T cells employing immunodominant HCMV antigens.
Given the fact that several hurdles remain to be conquered, recent clinical trials have outlined the feasibility of CMV-specific ACT prior to tumor recurrence with minimal adverse effects and a substantial improvement in median overall survival and progression-free survival. This review discusses the role of HCMV in gliomagenesis, disease prognosis, and recent breakthroughs in harnessing HCMV-induced immunogenicity in the GB tumor microenvironment to develop effective CMV-specific ACT.
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