Caloric Restriction Impairs Regulatory T cells Within the Tumor Microenvironment After Radiation and Primes Effector T cells

Manukian, Gregor; Kivolowitz, Charles; DeAngelis, Tiziana; Shastri, Anuradha; Savage, Jason E.; Camphausen, Kevin; Rodeck, Ulrich; Zarif, Jelani C.; Simone, Nicole L.

doi:10.1016/j.ijrobp.2021.02.029

Cited by 28 publications

(25 citation statements)

References 43 publications

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“…7a, Supplementary Fig. 10a), matching prior findings in a 4T1 model subjected to 30% CR 45 . However, the frequency of CD8 + Foxp3 + Tregs (whose levels are correlated with poor outcome 44 ) showed a downward trend in daily CR-fed mice (Fig.…”

Section: Resultssupporting

confidence: 84%

“…Earlier work has suggested that upregulation of immune-fighting T-cells, specifically CD8 + and CD4 + , leads to slower tumor growth 17 and is a good indicator of survival outcome 67 . Conversely, depletion of CD8 + partially eliminates CR-mediated delay in tumor growth 45 . Here, our findings show that daily CR led to an increase in CD8 + and CD4 + cells in peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

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Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

et al. 2021

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Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.

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Section: Resultssupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

et al. 2021

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“…Additionally, CR can shape the tumor immune microenvironment by specifically decreasing the number of tumor associated macrophages, increasing the formation of a reservoir of CD8 + cytotoxic T cells and memory T cells while negative modulating immunosuppressive Treg cells' activity and immunosuppressive cytokines levels [41,42,46,47].…”

Section: Calorie Restriction and Cancer Progressionmentioning

confidence: 99%

Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy

et al. 2021

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Cancer is one of the most frequently diagnosed diseases, and despite the continuous efforts in searching for new and more effective treatments, its morbidity and mortality remain a significant health problem worldwide. Calorie restriction, a dietary manipulation that consists in a reduction of the calorie intake, is gaining attention as a potential adjuvant intervention for preventing and/ or fighting cancer. Several forms of energy reduction intake, which includes caloric restriction tout-court, dietary restrictions, and intermittent fasting, are being explored for their ability to prevent or slow down cancer progression. Additionally, another anti-cancer approach being under investigation relies on the use of nutraceuticals known as "Caloric Restriction Mimetics" that can provide caloric restriction-mediated benefits without subjecting the patients to a strict diet. Preclinical in vitro and in vivo studies consistently show that diet modifiers reducing the calorie have impact on tumor microenvironment and cancer metabolism, resulting in reduced growth and progression of cancer. Preliminary clinical studies show that patients subjected to a reduced nutrient/energy intake experience improved outcomes from chemo-and radiotherapy while better tolerating the side effects. Here, we review the state of the art on the therapeutic potential of calorie restriction and of caloric restriction mimetics in preventing or retarding tumor development by modulating a subset of cellular processes. The most recent clinical progresses with caloric restriction mimetics in the clinical practice are also discussed.

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“…CR was also shown to improve radiation therapy treatment in two aggressive breast cancer models, delaying metastasis and tumor growth, and increasing survival in comparison to the radiation therapy alone [98]. Another study using a murine triple-negative breast cancer model demonstrated that CR was capable of decreasing the number of intratumoral TILs and increasing the number of effector cells after radiation therapy [99].…”

Section: Caloric Restriction Dietmentioning

confidence: 98%

Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma

et al. 2021

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Osteosarcoma (OS) is the most frequent primary bone cancer, affecting mostly children and adolescents. Although much progress has been made throughout the years towards treating primary OS, the 5-year survival rate for metastatic OS has remained at only 20% for the last 30 years. Therefore, more efficient treatments are needed. Recent studies have shown that tumor metabolism displays a unique behavior, and plays important roles in tumor growth and metastasis, making it an attractive potential target for novel therapies. While normal cells typically fuel the oxidative phosphorylation (OXPHOS) pathway with the products of glycolysis, cancer cells acquire a plastic metabolism, uncoupling these two pathways. This allows them to obtain building blocks for proliferation from glycolytic intermediates and ATP from OXPHOS. One way to target the metabolism of cancer cells is through dietary interventions. However, while some diets have shown anticancer effects against certain tumor types in preclinical studies, as of yet none have been tested to treat OS. Here we review the features of tumor metabolism, in general and about OS, and propose avenues of research in dietary intervention, discussing strategies that could potentially be effective to target OS metabolism.

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Caloric Restriction Impairs Regulatory T cells Within the Tumor Microenvironment After Radiation and Primes Effector T cells

Cited by 28 publications

References 43 publications

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy

Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma

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