Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study

Quaglino, Pietro; Marenco, Federica; Osella‐Abate, Simona; Cappello, N.; Ortoncelli, Michela; Salomone, B.; Fierro, Maria Teresa; Savoia, Paola; Bernengo, Maria Grazia

doi:10.1093/annonc/mdp325

Cited by 167 publications

(160 citation statements)

References 30 publications

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“…Late-stage melanoma patients who spontaneously develop vitiligo benefit from a longer time to disease progression and a significantly increased lifespan (9). Mouse melanoma models have echoed these findings, with the most potent immunotherapies inducing both melanoma rejection and widespread vitiligo (17).…”

Section: Discussionmentioning

confidence: 99%

“…Vitiligo, or the autoimmune destruction of melanocytes, is a positive prognostic factor for melanoma patients (9)(10)(11). The condition affects approximately 3% of melanoma patients (9), although its incidence may be increased by immunotherapies such as IFN-α (12) and ipilimumab, which was recently shown to improve survival in patients with metastatic melanoma (13,14). Melanomaassociated vitiligo is manifested as depigmented patches of skin or hair, which are infiltrated with melanoma/melanocyte antigen-specific CD8 + T cells (15,16).…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

Byrne¹,

Côté²,

Zhang³

et al. 2011

J. Clin. Invest.

105

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A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship between these two phenomena remains unclear. In the present study we have found that vitiligo, the autoimmune destruction of melanocytes, generates self antigen required for mounting persistent and protective memory CD8 + T cell responses to melanoma. Vitiligo developed in approximately 60% of mice that were depleted of regulatory CD4 + T cells and then subjected to surgical excision of large established B16 melanomas. Mice with vitiligo generated 10-fold larger populations of CD8 + memory T cells specific for shared melanoma/melanocyte antigens. CD8 + T cells in mice with vitiligo acquired phenotypic and functional characteristics of effector memory, suggesting that they were supported by ongoing antigen stimulation. Such responses were not generated in melanocyte-deficient mice, indicating a requirement for melanocyte destruction in maintaining CD8 + T cell immunity to melanoma. Vitiligo-associated memory CD8 + T cells provided durable tumor protection, were capable of mounting a rapid recall response to melanoma, and did not demonstrate phenotypic or functional signs of exhaustion even after many months of exposure to antigen. This work establishes melanocyte destruction as a key determinant of lasting melanoma-reactive immune responses, thus illustrating that immune-mediated destruction of normal tissues can perpetuate adaptive immune responses to cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

Byrne¹,

Côté²,

Zhang³

et al. 2011

J. Clin. Invest.

105

View full text Add to dashboard Cite

show abstract

“…136 It is well known that the development of autoimmunity is associated with clinically effective cancer immunotherapy. 137 Thus, treatment of patients with anti-CTLA-4 antibodies has been shown to induce autoimmunity, which predicts clinical response in cancer settings. The development of autoimmunity was found to be an independent predictor of overall survival in patients with melanoma treated with IFN or IL-2.…”

Section: Immunological and Clinical Monitoring Of Cancer Vaccine-treamentioning

confidence: 99%

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

Селедцов

Гончаров

Селедцова

2015

Human Vaccines & Immunotherapeutics

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“…2 The presence of these T cells is usually not associated with autoimmunity, even though approximately 3% of melanoma patients develop vitiligo-like skin hypopigmentation. 4 The lymphocytes infiltrating these lesions were reported to be mostly CD8 þ T cells directed against differentiation antigens. 5 The antitumoral immune responses, either spontaneous or stimulated by immunotherapy, do not usually lead to complete eradication of melanoma, even when the recruitment of T cells to the tumor site is successful.…”

mentioning

confidence: 99%

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

Kholmanskikh

Baren

Brasseur

et al. 2010

Intl Journal of Cancer

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We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4-to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1b. This effect is NF-jB and JNKdependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1b reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1a or IL-1b secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that~13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

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Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study

Abstract: Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis.

Cited by 167 publications

References 30 publications

Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

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