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:Acute natural killer cells response to a continuous moderate intensity and a work-matched high intensity interval exercise session in metastatic cancer patients treated with chemotherapy.
Acute natural killer cells response to a continuous moderate intensity and a work-matched high intensity interval exercise session in metastatic cancer patients treated with chemotherapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
在转移性癌症患者接受化疗期间,MOD 和 HIIE 均能引发 NK 细胞的急性动员和外出,这些 NK 细胞表现出与高细胞毒性和肿瘤归巢相关的表型特征。未来需要开展纵向试验,以确定将有氧运动训练与化疗相结合是否能转化为有利的免疫和临床结局。
已有研究提示,有氧运动引起的急性自然杀伤(NK)细胞反应可能有助于解释临床前研究中观察到的规律运动的抑瘤效应。此外,由于该反应受运动强度调节,高强度间歇运动(HIIE)可能代表一种在癌症患者中具有前景的治疗方式。然而,这种免疫反应在目前正在接受化疗的癌症患者中尚未得到研究。
旨在描述接受化疗的转移性癌症患者在中强度持续有氧运动(MOD)和HIIE训练后急性NK细胞反应的特征。
12名癌症患者(45-65岁)以区组随机顺序接受了MOD和持续时间及做功匹配的HIIE试验。在每次试验前、试验后和试验后1h分离外周血单核细胞(PBMC)。使用流式细胞术和全血细胞计数对NK细胞亚群进行计数。评估细胞毒性NK细胞(cNK;CD56 dim CD16 +)亚群表面分化标志物CD57和CD158a、活化受体NKG2D、免疫检查点TIM-3和PD-1以及趋化因子受体CXCR3、CXCR4和CCR2的表达。
cNK细胞血液计数在MOD后立即增加(p < 0.001),并在运动停止1小时后下降回运动前水平(p < 0.001)。反应最显著的cNK细胞亚群表达CD57、CD158a、NKG2D、TIM-3和CXCR3。HIIE试验引发了类似的双相反应,试验之间无任何差异(所有p ≥ 0.38)。然而,在HIIE后观察到cNK细胞亚群中CXCR4和NKG2D的MFI值发生显著变化(所有p ≤ 0.038),而MOD后则未观察到。
It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therapeutic approach in cancer patients. However, this immune response remains unstudied in cancer patients currently undergoing chemotherapy.
To characterize the acute NK cell response following a moderate-intensity continuous aerobic exercise session (MOD), and a HIIE session in metastatic cancer patients treated with chemotherapy.
Twelve cancer patients (45-65 years old) underwent a MOD and a duration and work-matched HIIE trial, in a block-randomized order. Peripheral blood mononuclear cells (PBMC) were isolated before, after and 1h after each trial. NK cell subsets were enumerated using flow cytometry and complete blood counts. The surface expression of the cytotoxic NK cell (cNK; CD56 dim CD16 + ) subset was evaluated for its expression of the differentiation markers CD57 and CD158a, the activating receptor NKG2D, the immune checkpoints TIM-3 and PD-1, and the chemokine receptors CXCR3, CXCR4 and CCR2.
cNK cell blood counts increased immediately following MOD (p < 0.001) and decreased back to pre-exercise values 1 h after exercise cessation (p < 0.001). The most responsive cNK cell subsets were expressing CD57, CD158a, NKG2D, TIM-3 and CXCR3. The HIIE trial elicited a similar biphasic response, without any difference between trials (all p ≥ 0.38). However, significant changes in the MFI values of CXCR4 and NKG2D were observed in the cNK cell subset following HIIE (all p ≤ 0.038), but not MOD.
In metastatic cancer patients undergoing chemotherapy, both MOD and HIIE can elicit an acute mobilisation and egress of NK cells exhibiting phenotypic characteristics associated with high cytotoxicity and tumor homing. Future longitudinal trials are needed to determine if combining aerobic exercise training and chemotherapy will translate towards favorable immune and clinical outcomes.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。