Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

Calorie restriction or dietary restriction: how far they can protect the brain against neurodegenerative diseases?

Finding the correct nutritional intervention is one of the biggest challenges in treating patients with neurodegenerative diseases.In general,these patients develop strong metabolic alterations,resulting in lower treatment efficacy and higher mortality rates.However,there are still many open questions regarding the effectiveness of dietary interventions in neurodiseases.Some studies have shown that a reduction in calorie intake activates key pathways that might be important for preventing or slowing down the progression of such diseases.However,it is still unclear whether these neuroprotective effects are associated with an overall reduction in calories(hypocaloric diet)or a specific nutrient restriction(diet restriction).Therefore,here we discuss how commonly or differently hypocaloric and restricted diets modulate signaling pathways and how these changes can protect the brain against neurodegenerative diseases.