Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

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.

Extracellular vesicles and particles as mediators of long-range communication in cancer: connecting biological function to clinical applications.

Over the past decade, extracellular vesicles and particles (EVPs) have emerged as critical mediators of intercellular communication, participating in numerous physiological and pathological processes. In the context of cancer, EVPs exert local effects, such as increased invasiveness, motility, and reprogramming of tumor stroma, as well as systemic effects, including pre-metastatic niche formation, determining organotropism, promoting metastasis and altering the homeostasis of various organs and systems, such as the liver, muscle, and circulatory system. This review provides an overview of the critical advances in EVP research during the past decade, highlighting the heterogeneity of EVPs, their roles in intercellular communication, cancer progression, and metastasis. Moreover, the clinical potential of systemic EVPs as useful cancer biomarkers and therapeutic agents is explored. Last but not least, the progress in EVP analysis technologies that have facilitated these discoveries is discussed, which may further propel EVP research in the future.

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.