Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial

Morita, Makoto; Okuyama, Mai; Akutsu, Taisuke; Ohdaira, Hironori; Suzuki, Yutaka; Urashima, Mitsuyoshi

doi:10.3390/nu13061987

Cited by 18 publications

(15 citation statements)

References 28 publications

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“…Programmed death-ligand 1 (PD-L1) as an anticancer immunity counter expression of cancer cells, was found to be upregulated. PD-L1 was measured through ELISA, divided into five quintiles; and vit D supplementation was found to significantly reduce the risk of relapses and death to approximately 30% of the highest quantile of serum PD-L1 ( 89 ).…”

Section: Antioxidants Acting As Protumorigenicmentioning

confidence: 99%

The interplay between reactive oxygen species and antioxidants in cancer progression and therapy: a narrative review

Bekhet¹,

Eid²

2021

Transl Cancer Res TCR

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To unveil the role of reactive oxygen species (ROS) and antioxidants in signaling and involvement in cancer progression and therapy.Background: Cancer is considered one of the main causes of mortality in developed countries and expected to be more in developing countries as well. Although some cancers may develop at young age, yet almost all types of cancers are an accumulation of genetic and epigenetic cell damages. Cancer is considered a diverse collection of diseases on a cellular level rather than a single disease; and each disease has a different cause as well. ROS have been seen as harmful toxic molecules; however, they are recognized for cellular signaling capabilities. Elevated levels of ROS have protumorigenic activities; they induce cancer cell proliferation, and adaptation to hypoxia in addition to other effects like DNA damage and genetic instability.They are produced excessively by cancer cells to hyperactivate cellular transformation meanwhile increasing antioxidant capacity to avoid cell death.Methods: We discussed peer reviewed published research work from 1987 to 2021. In this paper, we review the role of antioxidants as defensive barrier against excessive ROS levels for maintaining oxidationreduction (redox) balance; however, antioxidant can also strive in tumor cells with their scavenging capacities and maintain protumorigenic signaling and resist the cancer cell oxidative stress and apoptosis. High doses of antioxidant compounds could be toxic to cells as they are capable of reacting with the physiological concentrations of ROS present for normal cellular processes and signaling.Conclusions: Maintaining cellular redox homeostasis is vital for healthy biological system. Therefore, therapeutic modalities for cancer including antioxidants and ROS management should be used at certain doses to target specific redox pathways involved in cancer progression without disrupting the overall redox balance in normal cells.

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Section: Antioxidants Acting As Protumorigenicmentioning

confidence: 99%

The interplay between reactive oxygen species and antioxidants in cancer progression and therapy: a narrative review

Bekhet¹,

Eid²

2021

Transl Cancer Res TCR

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Section: Resultsmentioning

confidence: 99%

“…One RCT found mixed results for vitamin D supplementation with 200 IU/day in patients with digestive-tract cancer, post-curative surgery [ 55 ]. The study found that the effect of supplementation depended on the levels of serum Programmed Death Ligand 1 (PD-L1), a regulatory molecule expressed in T cells with immunosuppressive function [ 55 ]. Since PD-L1 is associated with a poorer cancer prognosis in various types of cancer (gastric cancer, small cell lung cancer, pancreatic cancer, breast cancer) [ 83 , 84 , 85 , 86 ], for those patients in the lowest PD-L1 concentration quintile, vitamin D supplementation seemed to have a detrimental effect by upregulating serum PD-L1 levels; however, for those in the highest quintile, vitamin D was beneficial and downregulated serum PD-L1 levels [ 55 , 87 ].…”

Section: Resultsmentioning

confidence: 99%

A Narrative Review of the Safety of Anti-COVID-19 Nutraceuticals for Patients with Cancer

Bader-Larsen

Magkos

2021

Cancers

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Interest in dietary supplements and their efficacy in treating and preventing disease has increased greatly since the outbreak of the COVID-19 pandemic. Due to the risk of severe COVID-19 in patients with cancer, we conducted a narrative review aiming to better understand the data on the safety of the most efficacious “anti-COVID-19” nutraceuticals for patients with cancer. We conducted a PubMed database search aimed at identifying the most effective nutrients for use against COVID-19. For the identified nutraceuticals, we searched PubMed again regarding their safety for patients with cancer. Fifty-four total records (52 independent studies) were retrieved, pertaining to vitamin D, vitamin C, selenium, omega-3 fatty acids, and zinc. Vitamin D results from 23 articles indicated safe use, but two articles indicated potential harm. All 14 articles for vitamin C and five out of six articles for selenium indicated the safety of use (one study for selenium suggested harm with high-dose supplementation). Results for omega-3 fatty acids (seven articles) and zinc (one article), however, were rather mixed regarding safety. We conclude that vitamin D, vitamin C, and selenium supplements are likely safe or even beneficial at typically recommended doses; however, caution is urged with omega-3 fatty acid supplements, and zinc supplements should likely be avoided. More experimental research is needed, and nutraceutical use by patients with cancer should always be under the supervision of a healthcare team.

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“…It is still unclear why CD4 + , CD8 + T lymphocytes decrease in vitamin D deficiency and how these lymphocytes increase with vitamin D supplementation. However, in a recent study, Morita et al ( 2021 ) reported that vitamin D supplementation may have a bimodal function of increasing serum PD-L1 when serum PD-L1 levels are very low and decreasing serum PD-L1 levels when serum PD-L1 levels are very high. Presumably, vitamin D could increase the number of T lymphocytes by eliminating the suppressive effect of the PD-1 PD-L1 pathway on T lymphocytes.…”

Section: Covid-19 Pd-1/pd-l1 Signaling and Vitamin Dmentioning

confidence: 98%

Vitamin D can reduce severity in COVID-19 through regulation of PD-L1

Aygün

2022

Naunyn-Schmiedeberg's Arch Pharmacol

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COVID-19 is a highly contagious viral infection that has killed millions of people around the world. The most important diagnostic feature of COVID-19 is lymphocyte depletion, particularly the depletion of T cells. In COVID-19 infections, there is a link between destruction of T cells and increased expression of inhibitory immune checkpoint molecules (PD-1/PD-L1) on T cell surfaces. It was shown that PD-1/PD-L1 levels increase in severely COVID-19 infected individuals. Higher proinflammatory cytokine levels cause increased PD-1/PD-L1 expression. In severe COVID-19, higher proinflammatory cytokine levels may increase PD-1/PD-L1. Vitamin-D is an important immune regulator. It is known that the numbers of CD4 + and CD8 + T lymphocytes decrease in vitamin D deficiency while vitamin D supplementation increases CD + 4 lymphocytes. Vitamin D can increase regulatory T cell (Treg) activity. Vitamin D also has a diminishing effect on proinflammatory cytokines. In severe COVID-19 cases, vitamin D supplementation may inhibit the increase of PD-L1 expression through reducing proinflammatory cytokine levels. Thus, vitamin D supplementation could eliminate the suppressive effect of PD-L1 on CD4 + and CD8 + T cells, preventing lymphopenia and reducing disease severity and mortality in patients infected with COVID-19. Besides, vitamin D supplementation can reduce inflammation by increasing Treg activity. The aim of this letter is to discuss the functions of inhibitory immune checkpoint molecules and their effects on dysfunction and depletion of T-cells as well as to explain the possible modulatory effect of vitamin D on these checkpoints and T cells.

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Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial

Cited by 18 publications

References 28 publications

The interplay between reactive oxygen species and antioxidants in cancer progression and therapy: a narrative review

The interplay between reactive oxygen species and antioxidants in cancer progression and therapy: a narrative review

A Narrative Review of the Safety of Anti-COVID-19 Nutraceuticals for Patients with Cancer

Vitamin D can reduce severity in COVID-19 through regulation of PD-L1

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