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:Investigating the impact of exercise on T and NK cells in skin cancer: a systematic review.
Investigating the impact of exercise on T and NK cells in skin cancer: a systematic review.
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皮肤癌在所有癌症中发病率最高,且黑色素瘤和非黑色素瘤皮肤癌的发病率均在上升。需要适合其管理的替代辅助治疗策略。可改变的生活方式因素会影响疾病结局,或改善或恶化结局。运动是可改变生活方式因素的一个例子,可作为其他癌症类型的辅助疗法来改善免疫功能和整体临床结局。本综述最初旨在探讨运动对皮肤癌临床/疾病结局产生影响的T细胞特异性机制。研究质量采用改良的Covidence质量评估模板及动物模型研究特定标准进行评估。共纳入10篇文章;所有文章均为研究黑色素瘤的小鼠模型研究。八项研究(n=8)采用随机对照试验设计,两项为生物信息学研究,一项研究使用人类数据,可强化与人类健康的联系。虽然本综述最初聚焦于T细胞,但许多研究报告了NK细胞的显著变化,且由于NK细胞与T细胞共享相同的造血谱系/共同淋巴祖细胞,这些数据被纳入分析。大多数研究表明运动减轻了黑色素瘤肿瘤负荷。在黑色素瘤接种前进行运动对于延迟癌变和减轻肿瘤负荷最为有效。协同作用是研究中发现的一个主题;PD-1/PD-L1治疗与运动不具有协同作用。相反,运动与精神刺激具有协同作用,且进行运动时的温度显著减轻了肿瘤负荷。多项小鼠研究报道,运动可改善黑色素瘤的临床结局,且长期运动在减轻肿瘤负荷方面更为有效。仍需进一步研究以探讨这一关系在人类及其他类型皮肤癌中的表现。
Skin cancer has the highest incidence of all cancers, and their incidence are increasing in both melanoma and non-melanoma skin cancers. Alternative adjuvant treatment strategies appropriate for their management are needed. Modifiable lifestyle factors influence disease outcomes, either improving or worsening outcomes. Exercise is an example of a modifiable lifestyle factor, and can be prescribed as an adjuvant therapy in other cancer types to improve immune function and overall clinical outcomes. The initial aim of the review was to investigate the T-cell specific mechanisms of exercise which affect clinical/disease outcomes in skin cancer. Study quality was assessed by a modified Covidence quality assessment template with animal-model study specific criteria. A total of 10 articles were included; all articles were murine model studies investigating melanoma.
Eight studies (n=8) employed a randomised controlled trial design, with two bio-informatics studies, and one study using human data which could solidify a link to human health. While the review focussed initially on T-cells, many studies reported significant changes in NK cells, and as they share the same haematopoietic lineage/ common lymphoid progenitor as T cells, the data was included in the analyses. Most studies indicated that exercise reduced melanoma tumour burden.
Exercising prior to melanoma inoculation was most effective for delaying carcinogenesis and reducing tumour burden. Synergism was a topic identified in studies; PD-1/PD-L1 treatment, and exercise were not synergistic. Conversely, exercise and mental stimulation were synergistic, and the temperature at which exercise was conducted significantly reduced tumour burden. Several murine studies reported that exercise improved clinical outcomes in melanoma, and that long-term exercise was more effective in reducing tumour burden.
Further studies are required to investigate this relationship in humans, and in other types of skin cancer.
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