Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy

Chen, Huiqing; Ma, Fengwang; Xiao, Chen-Lin; Sun, Bao; Liu, Yiping; Tang, Haoneng; Yang, Yue; Liu, Wenhui; Luo, Zhicheng

doi:10.3389/fimmu.2022.937476

Cited by 5 publications

(10 citation statements)

References 41 publications

(42 reference statements)

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“…However, the 25(OH)D level of non-PR patients was only 16.28±5.99 ng/mL, that is, VitD insufficient, suggesting that sufficient VitD is associated with improved efficacy. 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.…”

Section: Discussionmentioning

confidence: 97%

“…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: 99%

“…Indeed, a recent clinical study showed higher baseline VitD levels in ICI responders and that certain single nucleotide polymorphisms related to VitD metabolism might be biomarkers of ICI response. 22 The underlying mechanisms of VitD and immunotherapy responses have been explored. VitD has also been shown to be related to immune checkpoints such as PD-1 and PD-L1; serum VitD levels are negatively correlated with PD-1 expression on CD8 + T cells in NSCLC patients, 27 which might provide a target-mediated mechanism of VitD efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is rational to speculate that VitD also plays a role in clinical outcomes from cancer immunotherapy. Indeed, a recent clinical study showed higher baseline VitD levels in ICI responders and that certain single nucleotide polymorphisms related to VitD metabolism might be biomarkers of ICI response 22…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…In light of all such studies, it becomes evident that additional factors are involved in bringing about the supportive role of Vitamin D to innate anti-microbial immune response. Further studies with sufficient sample size are required in this purview, which might include the role of other nutrients in complementing Vitamin D in preventing TB relapse, as well as the role of genetic polymorphisms in genes involved in the Vitamin D metabolism and Vitamin D Receptor polymorphism in bringing about a differential therapeutic effect in such subjects [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial

et al. 2023

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Background The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. Methods This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15–60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. Results A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. Conclusions The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. Trial registration CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

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Regulatory role of the programmed cell death 1 signaling pathway in sepsis induced immunosuppression

Zhong

Yin

2023

Front. Immunol.

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Sepsis is a multiple organ dysfunction syndrome caused by the host’s immune response to infection, with extremely high incidence and mortality. Immunosuppression is an essential pathophysiological alteration that influences the clinical treatment and prognosis of sepsis. Recent studies have suggested that the programmed cell death 1 signaling pathway is involved in the formation of immunosuppression in sepsis. In this review, we systematically present the mechanisms of immune dysregulation in sepsis and elucidate the expression and regulatory effects of the programmed cell death 1 signaling pathway on immune cells associated with sepsis. We then specify current research developments and prospects for the application of the programmed cell death 1 signaling pathway in immunomodulatory therapy for sepsis. Several open questions and future research are discussed at the end.

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Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy

Cited by 5 publications

References 41 publications

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

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial

Regulatory role of the programmed cell death 1 signaling pathway in sepsis induced immunosuppression

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