Low Vitamin D Status Predicts Poor Clinical Outcome in Advanced Melanoma Treated With Immune Checkpoint or BRAF/MEK Inhibitors: A Prospective Non-Interventional Side-by-Side Analysis

Reichrath, Jörg; Biersack, Florian; Wagenpfeil, Stefan; Schöpe, Jakob; Pföhler, Claudia; Saternus, Roman; Vogt, Thomas

doi:10.3389/fonc.2022.839816

Cited by 10 publications

(10 citation statements)

References 28 publications

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“…Late responders also reported a trend toward higher values of PUFA energy intake share, vitamin D and anthocyanin consumption, as well as lower reported intake of saturated fatty acid use compared to early responders, which was all previously associated with potentially beneficial effects on the cancer treatment [51,[55][56][57][58][59][60]. A higher use of alcohol was reported in late responders; while chronic alcoholism was linked with the development of various cancers, a potential of alcohol to activate dendritic and natural killer cells and potentially increase PD-L1 protein expression in tumor tissue was also reported [61,62].…”

Section: Discussionmentioning

confidence: 88%

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy

Golčić

Simetić

Herceg

et al. 2023

Cancers

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Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.

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Section: Discussionmentioning

confidence: 88%

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy

Golčić

Simetić

Herceg

et al. 2023

Cancers

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“…22 Another study also implicated that even an increase in 25(OH)D of only 1 ng/mL was associated with an up to 3.9% reduced risk for tumor progression. 23 This difference was more pronounced in the irAE subgroup. IrAEs occur as a consequence of immune system overactivation, so irAEs are thought to occur in the face of better treatment responses.…”

Section: Discussionmentioning

confidence: 91%

“…A recent study also indicated that patients with higher plasma 25(OH)D levels had a better treatment response, though there was only a limited number of ICI responders in that study 22. Another study also implicated that even an increase in 25(OH)D of only 1 ng/mL was associated with an up to 3.9% reduced risk for tumor progression 23. This difference was more pronounced in the irAE subgroup.…”

Section: Discussionmentioning

confidence: 92%

Vitamin D Status Is Associated With Immune Checkpoint Inhibitor Efficacy and Immune-related Adverse Event Severity in Lung Cancer Patients: A Prospective Cohort Study

You

Liu

Tang

et al. 2023

Journal of Immunotherapy

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Vitamin D (VitD) is potentially immunomodulatory, so here we aimed to explore the relationships between serum VitD levels, immune checkpoint inhibitor (ICI) efficacy, and immunerelated adverse events (irAEs). Serum 25-hydroxyvitamin D [25 (OH)D] levels were quantified before and after ICI treatment in prospectively enrolled patients with advanced lung cancers. Of 77 enrolled patients, 29 developed 42 irAEs. Baseline 25(OH)D levels of partial response (PRs) patients were significantly higher than non-PR patients (19.39 ± 7.16 vs. 16.28 ± 5.99 ng/mL, P = 0.04). The area under the curve of 25(OH)D > 15.73 ng/mL to identify PR was 0.63 (95% CI, 0.51-0.76, P = 0.047), and baseline 25(OH)D levels > 15.73 ng/mL (odds ratio: 2.93, 95% CI, 1.10-7.79, P = 0.03) and prior targeted therapy (odds ratio: 0.30, 95% CI, 0.10-0.92, P = 0.04) were independent predictors of PR as best efficacy by multivariable logistic regression. With respect to irAEs, baseline 25 (OH)D levels were higher in grade 1 irAE patients than in grade 2/3/4 irAE patients (20.07 ± 8.64 vs. 15.22 ± 2.30 ng/mL, P = 0.02). However, the area under the curve was only 0.56 (95% CI, 0.42-0.70, P = 0.39) for a baseline 25(OH)D of 20.99 ng/mL for predicting irAE occurrence. There was a direct monotonic relationship and U-shaped relationship between baseline 25(OH)D levels and ICI efficacy and irAE occurrence, respectively. Overall survival was significantly different between VitD sufficient, insufficient, and deficient patients (log-rank P = 0.01), which remained after adjustment in Cox proportional hazards regression models. Baseline 25(OH)D levels seem to be associated with ICI efficacy and prognosis, it might be helpful to assess the baseline VitD status, and supplementation with VitD might bring some benefit to enhance ICI efficacy and reduce moderate-severe irAEs.

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“…CYP27B1 was identified in human melanoma tumor tissue [61]. CYP27B1 expressions have been reported to be inversely correlated with the development of melanoma, and low or undetectable levels have been linked to poor prognosis [62,63]. CYP24A1, the most prominent catabolic enzyme, has been detected in tissues expressing VDR and plays a vital role in the local regulation of vitamin D activity [36].…”

Section: Dermal Expression Of Vitamin D-related Cyp Enzymesmentioning

confidence: 99%

Vitamin D in Melanoma: Potential Role of Cytochrome P450 Enzymes

Ben-Eltriki,

Gayle,

Paras

et al. 2024

Life

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Vitamin D is a promising anticancer agent for the prevention and treatment of several cancers, including melanoma. Low 25-hydroxyvitamin D levels, a routinely used marker for vitamin D, have been suggested as one of the factors in the development and progression of melanoma. The parent vitamin D needs activation by cytochrome P450 (CYP) enzymes to exert its actions via the vitamin D receptor (VDR). This review discusses the role of vitamin D in melanoma and how CYP-mediated metabolism can potentially affect the actions of vitamin D. Through interacting with the retinoid X receptor, VDR signaling leads to anti-inflammatory, antioxidative, and anticancer actions. Calcitriol, the dihydroxylated form of vitamin D3, is the most active and potent ligand of VDR. CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, whereas CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes and eventually cause lower levels of vitamin D and its active metabolites in tissues. Although the role of vitamin D in the development of melanoma is yet to be fully elucidated, it has been proposed that melanoma prevention may be significantly aided by increased vitamin D signaling. Furthermore, selective targeting of the catabolic enzymes responsible for vitamin D degradation could be a plausible strategy in melanoma therapy. Vitamin D signaling can be improved by utilizing dietary supplements or by modulating CYP metabolism. A positive association exists between the intake of vitamin D supplements and improved prognosis for melanoma patients. Further investigation is required to determine the function of vitamin D supplementation and specific enzyme targeting in the prevention of melanoma.

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Low Vitamin D Status Predicts Poor Clinical Outcome in Advanced Melanoma Treated With Immune Checkpoint or BRAF/MEK Inhibitors: A Prospective Non-Interventional Side-by-Side Analysis

Cited by 10 publications

References 28 publications

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy

Vitamin D Status Is Associated With Immune Checkpoint Inhibitor Efficacy and Immune-related Adverse Event Severity in Lung Cancer Patients: A Prospective Cohort Study

Vitamin D in Melanoma: Potential Role of Cytochrome P450 Enzymes

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