Exercise Medicine Research Institute, Edith Cowan University, Perth, Western Australia, Australia.
School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
Exerc Immunol Rev. 2024;30:26-48.
Conventional chemotherapies can stimulate the immune system by increasing tumour antigenicity (e.g., neoantigen exposure to immune cells) and altering adjuvanticity in the tumour (e.g., danger associated molecular patterns and cytokines). These molecules promote the recruitment, activation, and maturation of dendritic cells, which in turn, prime and activate cytotoxic T cells against tumour cells. However, several factors can decrease the immunostimulatory efficacy of chemotherapeutic agents. These include reduced tumour cell antigenicity and adjuvanticity and compromised immune function at a local and systemic level. Findings from preclinical studies show that dietary restriction and exercise promote systemic changes that may help to restore immune system function through several mechanisms, including an enhanced infiltration and function of antitumoral immune cells and a decrease in immunosuppressive cells, leading to a reduction in tumour volume. In addition, dietary restriction and exercise training in mice have been shown to enhance the efficacy of chemotherapy. In human studies there is also emerging evidence that dietary restriction and exercise can impact the immune system towards a more antitumoral profile. In this review, we discuss the immunostimulatory effects of dietary restriction (caloric restriction and fasting) and exercise training in preclinical cancer models, and potential synergies with chemotherapy. We then review clinical studies assessing the effects of these interventions on immune-related endpoints and tumour responses. Finally, we propose that combining dietary restriction with exercise could be a promising strategy to increase chemotherapy efficacy.
传统的化疗可以通过增加肿瘤抗原性(例如,新抗原暴露于免疫细胞)和改变肿瘤的佐剂性(例如,危险相关分子模式和细胞因子)来刺激免疫系统。这些分子促进树突状细胞的募集、激活和成熟,进而针对肿瘤细胞对细胞毒性 T 细胞进行致敏和激活。然而,有几个因素可以降低化疗药物的免疫刺激效果。这些因素包括肿瘤细胞抗原性和佐剂性降低,以及局部和全身免疫功能受损。临床前研究的结果表明,饮食限制和运动促进了全身性变化,这些变化可能通过多种机制有助于恢复免疫系统功能,包括增强抗肿瘤免疫细胞的浸润和功能,以及减少免疫抑制细胞,从而导致肿瘤体积缩小。此外,在小鼠中进行的饮食限制和运动训练已被证明可以增强化疗的疗效。在人类研究中,也有越来越多的证据表明,饮食限制和运动可以使免疫系统向更抗肿瘤的表型转变。在这篇综述中,我们讨论了饮食限制(热量限制和禁食)和运动训练在临床前癌症模型中的免疫刺激作用,以及它们与化疗的潜在协同作用。然后,我们回顾了评估这些干预措施对免疫相关终点和肿瘤反应影响的临床研究。最后,我们提出,将饮食限制与运动相结合可能是提高化疗疗效的一种有前途的策略。
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