Shortly after the powerful role that immunotherapies play in the battle against cancer were discovered, we are wowed by new findings almost everyday in the field. It is not surprising that the effect of human immune systems could have on tumors are influenced by many other factors, given the how complex the immune system is. (Cancer types, mutation rates/neoantigen loads of the tumors, gut µbiota of individuals, tumor intrinsic signatures all count here.) However, I'm surprised when two new studies simultaneously suggested that fasting/ calorie restriction is an influencer of immune surveillance.
In the latest issue of Cancer Cell, Di Biase et al. and Pietrocola et al. both showed that mice undergoing calorie-restricted diet had improved tumor control performance compared with those that had normal food. Treating mice with calorie-restriction was even more effective when combined with traditional chemotherapies like mitoxantrone and doxorubicin. The finding stays true when tested in different cancer models including breast cancer, non-small cell lung cancer, colorectal cancer and melanoma line, suggesting that calorie-restricted diet could be applied to patients with various cancer types.
The two studies both connected the improved therapeutic effect to the enhanced immunogenicity of tumors, which resulted in more cytotoxic immune cells (i. e. CD8 positive T lymphocytes) infiltrating in the tumors. They provided rather different mechanisms to explain the phenomenon. Di Biase et al. found that tumors with calorie deprivation had down-regulated level of the stress-responsive enzyme heme oxygenase-1 (HO-1), which could otherwise be utilized by tumor cells to suppress immune function. Pietrocola et al. suggested that autophagy of tumor cells triggered by fasting provided the immunogenic materials that activated immune system. It is more likely that both theories are true to simultaneously contribute here.
As it is hard to let cancer patients to undergo fasting, it might be more feasible that caloric
In the latest issue of Cancer Cell, Di Biase et al. and Pietrocola et al. both showed that mice undergoing calorie-restricted diet had improved tumor control performance compared with those that had normal food. Treating mice with calorie-restriction was even more effective when combined with traditional chemotherapies like mitoxantrone and doxorubicin. The finding stays true when tested in different cancer models including breast cancer, non-small cell lung cancer, colorectal cancer and melanoma line, suggesting that calorie-restricted diet could be applied to patients with various cancer types.
The two studies both connected the improved therapeutic effect to the enhanced immunogenicity of tumors, which resulted in more cytotoxic immune cells (i. e. CD8 positive T lymphocytes) infiltrating in the tumors. They provided rather different mechanisms to explain the phenomenon. Di Biase et al. found that tumors with calorie deprivation had down-regulated level of the stress-responsive enzyme heme oxygenase-1 (HO-1), which could otherwise be utilized by tumor cells to suppress immune function. Pietrocola et al. suggested that autophagy of tumor cells triggered by fasting provided the immunogenic materials that activated immune system. It is more likely that both theories are true to simultaneously contribute here.
As it is hard to let cancer patients to undergo fasting, it might be more feasible that caloric
restriction mimetics will be added to the pharmacological plan of cancer patients. Besides further confirming the finding in other cancer models and uncovering underlying mechanisms, it is also interesting to see whether the strategy could also synergistically work with immunotherapies, e.g. PD-1 blockers.
References:
Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell 2016
Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell 2016
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