中等强度的有氧运动训练通过减少线粒体损失来改善 CD8 肿瘤浸润淋巴细胞效应器功能。
Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.
发表日期:2024 Jun 21
作者:
Vanessa Azevedo Voltarelli, Mariane Tami Amano, Gabriel Cardial Tobias, Gabriela Silva Borges, Ailma Oliveira da Paixão, Marcelo Gomes Pereira, Niels Olsen Saraiva Câmara, Waldir Caldeira, Alberto Freitas Ribeiro, Leo Edmond Otterbein, Carlos Eduardo Negrão, James Edward Turner, Patricia Chakur Brum, Anamaria Aranha Camargo
来源:
HEART & LUNG
摘要:
有氧运动训练 (AET) 已成为降低癌症死亡率的一种策略,然而,解释 AET 对肿瘤发展的机制仍不清楚。肿瘤通过产生免疫抑制微环境和 T 细胞功能受损来逃避免疫检测,这与 T 细胞线粒体损失有关。 AET 可改善线粒体含量和功能,因此我们测试了 AET 是否会调节肿瘤浸润淋巴细胞 (TIL) 中的线粒体代谢。 Balb/c 小鼠在注射 CT26 结肠癌细胞之前和直至肿瘤收获之前接受跑步机 AET 方案。评估组织缺氧、TIL 浸润和效应器功能,以及线粒体含量、形态和功能。 AET 减少肿瘤生长、提高生存率并减少肿瘤缺氧。 AET 促进 CD8 TIL 浸润、IFN-γ 和 ATP 产生增加,与这些细胞中线粒体损失减少相关。总的来说,AET 通过改善线粒体含量和功能来增加 CD8 TIL 效应器功能,部分地减少肿瘤生长。© 2024 作者。
Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.© 2024 The Authors.