Impact of physical activity and energy restriction on immune regulation of cancer.
Impact of physical activity and energy restriction on immune regulation of cancer.
复制标题
体育活动和能量限制对癌症免疫调节的影响。
DOI：
10.21037/tcr.2020.03.38
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发表时间：
2020-09
影响因子：
0.9
通讯作者：
Rogers CJ
中科院分区：
文献类型：
--
作者：
Xu Y;Rogers CJ
癌症是世界范围内的一个重大公共卫生问题。生活方式因素，如体重和身体活动（PA），显著影响癌症的风险和进展。有强有力的证据表明，PA降低了许多癌症类型的风险和死亡率，而肥胖则增加了风险和死亡率。在多种临床前模型中，非肥胖宿主的能量限制（ER）可显著降低肿瘤发生率，并降低人类体重和心脏代谢危险因素。新出现的数据表明，PA-和er诱导的炎症和免疫介质的变化可能有助于这些干预措施的癌症预防效果。我们进行了系统的文献检索，以确定在人类和动物模型中评估PA和ER对肿瘤和免疫结果影响的研究。总共确定了97项符合条件的研究（68项研究报告了PA干预，30项研究报告了ER干预）。31项研究通过乳腺癌（n=17, 55%）、胃肠道（n=6, 19%）、黑色素瘤（n=4, 13%）和其他几种癌症类型（n=4, 13%）的临床前癌症模型研究了PA对癌症免疫结果的影响。尽管研究设计存在异质性，但大多数研究（n=23, 74%）报告了PA对肿瘤预后的积极影响。37项临床研究调查了PA对癌症免疫结果的影响。没有报道肿瘤结果，因此在这些研究中仅评估了免疫结果。PA研究在乳腺癌（n= 22,59 %）、胃肠道（n= 5,14 %）、前列腺癌（n= 2,5 %）、食管癌（n= 1,3 %）、肺癌（n= 1,3 %）、白血病（n= 1,3 %）或混合癌症类型（n= 5,14 %）的患者中进行。22项研究调查了雌激素受体干预对癌症免疫结果的影响，使用临床前癌症模型，包括乳腺癌（n=5, 23%）、胃肠道（n=5, 23%）、肺癌（n=2, 9%）、肝癌（n=2, 9%）、胰腺癌（n=2, 9%）和其他几种癌症类型（n=6, 27%）。22项研究中有21项报告了ER对肿瘤预后的积极影响。六项临床研究调查了ER（联合PA）对超重或肥胖癌症患者肿瘤免疫结局的影响。其中五项是针对乳腺癌患者的，另一项是针对多种癌症类型的患者。在纳入的研究中，在多个组织区室（血液、脾脏、淋巴结和肿瘤）中评估了广泛的免疫学参数，包括免疫细胞表型和功能、细胞因子以及其他免疫和炎症标志物。临床前和临床研究结果表明，PA和ER对循环因子和全身免疫反应均有不同程度的影响。PA + ER改变肿瘤中的基因表达谱和免疫浸润，可能导致免疫抑制因子的减少。然而，需要进一步的研究来更好地了解PA和/或ER对免疫调节的影响，特别是在肿瘤微环境（TME）中的作用。
Cancer is a major public health issue worldwide. Lifestyle factors, such as body weight and physical activity (PA), significantly impact cancer risk and progression. There is strong evidence that PA reduces and obesity increases risk and mortality from numerous cancer types. Energy restriction (ER) in non-obese hosts significantly reduces tumor incidence in a variety of preclinical models, and reduces body weight and cardiometabolic risk factors in humans. Emerging data suggest that PA- and ER-induced changes in inflammatory and immune mediators may contribute to the cancer prevention effects of these interventions. A systematic literature search was conducted to identify studies that evaluated the impact of PA and ER on tumor and immune outcomes in humans and animal models. A total of 97 eligible studies were identified (68 studies reporting PA interventions and 30 studies reporting ER interventions). Thirty-one studies investigated the effect of PA on cancer immune outcomes using preclinical cancer models of breast (n=17, 55%), gastrointestinal (n=6, 19%), melanoma (n=4, 13%), and several other cancer types (n=4, 13%). Despite the heterogeneity in study designs, the majority of studies (n=23, 74%) reported positive effects of PA on tumor outcomes. Thirty-seven clinical studies investigated the effect of PA on cancer immune outcomes. None reported tumor outcomes, thus only immune outcomes were evaluated in these studies. PA studies were conducted in patients with breast (n=22, 59%), gastrointestinal (n=5, 14%), prostate (n=2, 5%), esophageal (n=1, 3%), lung (n=1, 3%) cancer, leukemia (n=1, 3%), or mixed cancer types (n=5, 14%). Twenty-two studies investigated the effect of ER interventions on cancer immune outcomes using preclinical cancer models including breast (n=5, 23%), gastrointestinal (n=5, 23%), lung (n=2, 9%), liver (n=2, 9%), pancreatic (n=2, 9%), and several other cancer types (n=6, 27%). Positive effects of ER on tumor outcomes were reported in 21 of 22 studies. Six clinical studies investigated the effect of ER (in combination with PA) on tumor immune outcomes in cancer patients with overweight or obesity. Five were conducted in breast cancer patients, and one recruited patients of a mix of cancer types. A wide range of immunological parameters including immune cell phenotype and function, cytokines, and other immune and inflammatory markers were assessed in multiple tissue compartments (blood, spleen, lymph nodes and tumor) in the included studies. Results from preclinical and clinical studies suggest that both PA and ER exert heterogeneous effects on circulating factors and systemic immune responses. PA + ER alters the gene expression profile and immune infiltrates in the tumor which may result in a reduction in immune suppressive factors. However, additional studies are needed to better understand the effect of PA and/or ER on immunomodulation, particularly in the tumor microenvironment (TME).