RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines.
Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines.
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头颈部鳞状细胞癌(HNSCC)起源于口腔、下咽部、口咽部或喉部的上皮。HNSCC的潜在危险因素包括吸烟、饮酒、咀嚼槟榔、营养不良、口腔卫生不佳、人乳头瘤病毒(HPV)和EB病毒感染,以及白色念珠菌感染。HNSCC的发生与环境因素和基因突变均有关,其中基因突变对肿瘤进展的作用更为关键。上皮细胞发生的分子改变包括抑癌基因失活和原癌基因过表达,进而导致肿瘤细胞增殖和远处转移。HNSCC患者的树突状细胞(DC)和自然杀伤(NK)细胞功能受损,免疫抑制分子生成增加,调节性T细胞、共刺激分子及主要组织相容性复合体(MHC)分子减少,淋巴细胞亚群数量降低,且对抗原呈递细胞的应答较差。目前,HNSCC的标准治疗包括手术、化疗、放疗及其联合治疗。尽管过去数十年新型治疗方式不断发展,患者生存率仍未提高。要建立有效的免疫治疗,需要进一步了解免疫系统与HNSCC之间的相互作用,并亟须开发新的治疗方案。治疗性肿瘤疫苗被认为有望通过诱导强效适应性免疫应答、清除癌细胞来改善结局。与其他疫苗相比,肽类肿瘤疫苗具有更强的免疫原性和特异性。近年,针对HNSCC的肽类疫苗取得了显著进展。本文综述HNSCC的最新分子改变,探讨其免疫应答,并讨论肽类癌症疫苗策略的最新进展,同时指出肽类疫苗领域值得开展的未来研究方向。
Head and neck squamous cell carcinoma (HNSCC) arises from the epithelial lining of the oral cavity, hypopharynx, oropharynx, and larynx. There are several potential risk factors that cause the generation of HNSCC, including cigarette smoking, alcohol consumption, betel quid chewing, inadequate nutrition, poor oral hygiene, HPV and Epstein-Barr virus, and Candida albicans infections. HNSCC has causative links to both environmental factors and genetic mutations, with the latter playing a more critical role in cancer progression. These molecular changes to epithelial cells include the inactivation of cancer suppressor genes and proto-oncogenes overexpression, resulting in tumour cell proliferation and distant metastasis. HNSCC patients have impaired dendritic cell (DC) and natural killer (NK) cell functions, increased production of higher immune-suppressive molecules, loss of regulatory T cells and co-stimulatory molecules and major histocompatibility complex (MHC) class molecules, lower number of lymphocyte subsets, and a poor response to antigen-presenting cells.
At present, the standard treatment modalities for HNSCC patients include surgery, chemotherapy and radiotherapy, and combinatorial therapy. Despite advances in the development of novel treatment modalities over the last few decades, survival rates of HNSCC patients have not increased. To establish effective immunotherapies, a greater understanding of interactions between the immune system and HNSCC is required, and there is a particular need to develop novel therapeutic options.
A therapeutic cancer vaccine has been proposed as a promising method to improve outcome by inducing a powerful adaptive immune response that leads to cancer cell elimination. Compared with other vaccines, peptide cancer vaccines are more robust and specific. In the past few years, there have been remarkable achievements in peptide-based vaccines for HNSCC patients.
Here, we summarize the latest molecular alterations in HNSCC, explore the immune response to HNSCC, and discuss the latest developments in peptide-based cancer vaccine strategies. This review highlights areas for valuable future research focusing on peptide-based cancer vaccines.
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