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

Lommerts, Janny E; Bekkenk, Marcel W.; Luiten, Rosalie M.

doi:10.1080/14740338.2021.1915279

Cited by 31 publications

(32 citation statements)

References 39 publications

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“…On the other hand, autoimmunity may also have a protective role. In fact, patients undergoing an autoimmune reaction against melanocytes, such as vitiligo patients, show either a lower risk of developing melanoma [ 27 , 28 ] or a better prognosis [ 29 , 30 ], most likely due to a so-called “beneficial autoimmunity” [ 31 ]. The present study investigated the hypothesis that the expression of genes directly involved in autoimmunity may be altered in melanoma patients and may therefore represent suitable molecular targets for possible diagnostic, prognostic or therapeutic applications.…”

Section: Discussionmentioning

confidence: 99%

Expression of Autoimmunity-Related Genes in Melanoma

Scatozza

Facchiano

2022

Cancers

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(1) Background. Immune response dysregulation plays a key role in melanoma, as suggested by the substantial prognosis improvement observed under immune-modulation therapy. Similarly, the role of autoimmunity is under large investigation in melanoma and other cancers. (2) Methods. Expression of 98 autoimmunity-related genes was investigated in 1948 individuals (1024 melanoma and 924 healthy controls). Data were derived from four independent databases, namely, GEO in the selection phase, and Ist Online, GEPIA2 and GENT2, in three sequential validation-steps. ROC analyses were performed to measure the ability to discriminate melanoma from controls. Principal Component Analysis (PCA) was used to combine expression data; survival analysis was carried out on the GEPIA2 platform. (3) Results. Expression levels of NOD2, BAX, IL-18 and ADRB2 were found to be significantly different in melanoma vs. controls and discriminate melanoma from controls in an extremely effective way, either as single molecules (AUC > 0.93 in all cases) or as a profile, according to the PCA analysis. Patients showing high-expression of NOD2 and of IL-18 also show a significant survival improvement as compared to low-expression patients. (4) Conclusions. Four genes strongly related to autoimmunity show a significant altered expression in melanoma samples, highlighting the role they may play in melanoma.

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Section: Discussionmentioning

confidence: 99%

Expression of Autoimmunity-Related Genes in Melanoma

Scatozza

Facchiano

2022

Cancers

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“…Nevertheless, it happens that impaired function of T reg in the skin leads to the formation of T RM cells with autoimmune activity. To confirm this hypothesis, it was observed that the checkpoint inhibitor therapy used in patients with melanoma is associated with an increase in vitiligo disease (169,225).…”

Section: T Rm Cells and Autoimmune Diseasementioning

confidence: 98%

Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells

et al. 2022

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The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.

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“…Vitiligo is caused by destruction of melanocytes and is characterized by well-defined, hypopigmented macules that often coalesce into patches. 3,69 Vitiligo occurs in up to 16% of patients with melanoma, either Violaceous/erythematous, pruritic papules and plaques 19 Innate immune system activation leading to a Th1 response. 48 Decreased Tregs 48 Lichenoid reactions have also been reported in response to proton pump inhibitors, b-blockers and anti-TNF-a agents 47 Psoriasiform reactions ~4% of all cutaneous irAEs 50 Well-demarcated, scaly, erythematous plaques 22 Increased expression of IL-17 secondary to alteration of Th1 and Th17 pathways.…”

Section: Melanocyte Changesmentioning

confidence: 99%

“…65 Upregulation of C1r/C1s and TLR 4 (innate immune system) 67 All reported cases of BP irAE have been in patients treated with PD-(L) 1 inhibitors. 63 BP has also been reported in response to DPP-4 inhibitors, spironolactone and furosemide 99 Vitiligo ICI-associated and/or spontaneous vitiligo observed in up to 16% of patients with melanoma 70 Well-defined, hypopigmented macules that often coalesce into patches 69 Increased CXCR3 and CXCL10. 74 Tissue-resident memory T cells.…”

Section: Melanocyte Changesmentioning

confidence: 99%

Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

Seervai

Sinha

Kulkarni

2022

Clinical and Experimental Dermatology

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The discovery of immune checkpoint inhibition (ICI) sparked a revolution in the era of targeted anticancer therapy. However, although monoclonal antibodies targeting the cytotoxic T-lymphocyte antigen-4 and programmed death-1 axes have improved survival in patients with advanced cancers, these immunotherapies are associated with a wide spectrum of dermatological immune-related adverse events (irAEs), ranging from mild to life-threatening. Several publications have addressed the clinical and histopathological classification of these skin-directed irAEs, their impact on anti-tumour immunity and survival, and the critical role of supportive oncological dermatology in their management. In this paper, we review the current understanding of the mechanistic drivers of immune-related skin toxicities with a focus on inflammatory, immunobullous and melanocyte/pigment-related reactions. We detail the specific immune-based mechanisms that may underlie different cutaneous reactions. We also discuss potential mechanisms as they relate to extracutaneous irAEs and the lessons learned from these, the potential overlap with cutaneous irAEs, techniques to study differences in immune-related vs. de novo skin reactions, and how treatment of these AEs impacts cancer treatment, patient quality of life and overall survival. An improved understanding of the mechanistic basis of cutaneous irAEs will allow clinicians to develop and use blood-based biomarkers that could help ultimately predict onset and/or severity of these irAEs, and to implement rational mechanistic-based treatment strategies that are targeted to the irAEs while potentially avoiding reducing the anti-tumour effect of ICIs.

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

Cited by 31 publications

References 39 publications

Expression of Autoimmunity-Related Genes in Melanoma

Expression of Autoimmunity-Related Genes in Melanoma

Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells

Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

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