Epidemiological evidence suggests that exercise improves survival in cancer patients. However, much is still unknown regarding the mechanisms of this positive survival effect and there are indications that exercise may not be universally beneficial for cancer patients. The key to understanding in which situations exercise is beneficial may lie in understanding its influence on the tumour microenvironment (TME)-and conversely, the influence of the tumour on physical functioning. The TME consists of a vast multitude of different cell types, mechanical and chemical stressors and humoral factors. The interplay of these different components greatly influences tumour cell characteristics and, subsequently, tumour growth rate and aggression. Exercise exerts whole-body physiological effects and can directly and indirectly affect the TME. In this chapter, we first discuss the possible role of exercise capacity ('fitness') and exercise adaptability on tumour responsiveness to exercise. We summarise how exercise affects aspects of the TME such as tumour perfusion, vascularity, hypoxia (reduced oxygenation) and immunity. Additionally, we discuss the role of myokines and other circulating factors in eliciting these changes in the TME. Finally, we highlight unanswered questions and key areas for future research in exercise oncology and the TME.

Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells.

The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.

The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin (ADIPO) and leptin (LEP) are altered with adiposity and exert antagonistic effects on cancer cell proliferation. We set out to determine whether altering adiposity in-vivo via high fat diet (HFD) feeding changed the tumor growth supporting nature of adipose tissue and if voluntary physical activity (VPA) could ameliorate these HFD-dependent effects. We show that conditioned media (CM) created from the adipose tissue of HFD fed animals caused an increase in the proliferation of MCF7 cells compared to cells exposed to CM prepared from the adipose of lean chow diet fed counterparts. This increased proliferation was driven within the MCF7 cells by an HFD-dependent antagonism between AMPK and Akt signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of AdiporR1. VPA can ameliorate these proliferative effects of HFD-CM on MCF7 cells, increasing p27(T198) by AMPK, reducing pAkt(T308) and increasing AdipoR1, resulting in cell cycle withdrawal in a manner that depends on the VPA intensity. High physical activity (>3 km/day) completely abolished the effects of HFD feeding. In addition, AdipoR1 overexpression mimics the effects of exercise, abolishing the proliferative effects of the HFD-CM on MCF7 cells and further enhancing the anti-proliferative effects physical activity on the HFD-CM. Thus, VPA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients.