Vitiligo under anti–programmed cell death-1 therapy is associated with increased survival in melanoma patients

Nardin, Charlée; Jeand'heur, Anne; Bouiller, Kévin; Valnet-Rabier, Marie Blanche; Dresco, F.; Castagna, J.; Mareschal, Adrien; Carlet, Clémentine; Nerich, Virginie; Limat, Samuel; Puzenat, E.; Aubin, F.

doi:10.1016/j.jaad.2019.11.017

Cited by 28 publications

(35 citation statements)

References 5 publications

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“…Furthermore, the mRNA and protein expression of SFRP5 was significantly increased in PIG3V cells compared with that in PIG1 cells. Emerging evidences highlight that vitiligo has an inverse relationship with malignant melanoma, 52 , 53 , 54 , 55 , 56 which is consistent with our results.…”

Section: Discussionsupporting

confidence: 93%

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

et al. 2021

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Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/β-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the β-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

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Section: Discussionsupporting

confidence: 93%

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

et al. 2021

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“…In fact, when the vaccines did not work, there was no depigmentation (Bae et al, 2019;Luiten et al, 2005). Authors noted that patients with metastatic melanoma treated with checkpoint inhibitors often developed depigmentation, as reported in case studies (Nardin et al, 2019). This depigmentation may mimic vitiligo or may have a different photodistribution pattern (Figure 2b).…”

Section: Other Immunosuppressive Drugs In Vitiligo? the Case For Jak Inhibitorsmentioning

confidence: 87%

Vitiligo: Targeted Therapies Add Color to Disease Pathophysiology

Ezzedine

Vance

Hamzavi

et al. 2020

Journal of Investigative Dermatology

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There is excitement in the air for patients with vitiligo. For the first time in decades, we have early case studies showing that targeted therapies can repigment vitiliginous skin, and well-powered clinical trials are underway. However, at the time of this writing, there is no Food and Drug Administrationeapproved drug for vitiligo. In a randomized clinical trial by Khemis et al. report negative results on a randomized clinical trial testing the combination of apremilast, a phosphodiesterase 4 inhibitor, and narrowband-ultraviolet B versus placebo and narrowband-ultraviolet B in patients with nonsegmental vitiligo. The results of this trial are a reminder that clinical management of vitiligo is challenging at best, even when combining anti-inflammatory and/or immunomodulating agents with repigmenting agents. However, these negative trials are critical in improving our understanding of this complex and disfiguring disease.

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“…The occurrence of vitiligo in melanoma patients treated with anti-PD-1 agents is independently associated with better response rates and overall survival. [37,38] Other studies reporting on the development of several skin reactions, including vitiligo, show a 40-50% less risk of disease progression or death in melanoma patients developing skin reactions and receiving PD-1 therapy [36,39]. Despite the promising results with ICI, the overall response rates of advanced melanoma patients are still low or moderate.…”

Section: Good Prognostic Signmentioning

confidence: 99%

Vitiligo induced by immune checkpoint inhibitors in melanoma patients: an expert opinion

Lommerts

Bekkenk

Luiten

2021

Expert Opinion on Drug Safety

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Introduction: Treatment with immune checkpoint inhibitors in melanoma patients can cause immunerelated adverse effects, such as vitiligo. In vitiligo, specific autoimmunity against melanocytes results in depigmentation of the skin. Melanoma-associated vitiligo occurring in melanoma patients treated with immune checkpoint inhibitors can be seen as a good prognostic sign as higher survival rates in melanoma-associated vitiligo cases have been reported.Areas covered: This review gives an insight into the pathophysiology, clinical presentation, and management of melanoma-associated vitiligo caused by immune checkpoint inhibitors. Expert opinion: Development of melanoma-associated vitiligo induced by immune checkpoint inhibitors could be a good clinical marker for response and overall survival. Induction of vitiligo in these patients could also potentially lead to better response and survival rates. Further research should focus on several aspects of melanoma-associated vitiligo, such as better screening and registration, more understanding of pathophysiology of the type of immune response and the predictive value of melanoma-associated in patients treated with immune checkpoint inhibitors.

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Vitiligo under anti–programmed cell death-1 therapy is associated with increased survival in melanoma patients

Cited by 28 publications

References 5 publications

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

Vitiligo: Targeted Therapies Add Color to Disease Pathophysiology

Vitiligo induced by immune checkpoint inhibitors in melanoma patients: an expert opinion

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