New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

Byrne, Katelyn T.; Turk, Mary Jo

doi:10.18632/oncotarget.323

Cited by 91 publications

(61 citation statements)

References 85 publications

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“…91 For instance, vitiligo is a wellknown phenomenon in the immune response to melanoma and is due to shared melanocyte/melanoma antigens -meaning that antigens are presented on both, the healthy melanocyte and the dedifferentiated melanoma cell. 92,93 In the setting of melanoma immunotherapy, the rate of autoimmunity correlates with cancer regression and this side effect occurs in a non-essential organ. Thus, vitiligo poses only a relative concern when being confronted with a life-threatening disease.…”

Section: 87mentioning

confidence: 99%

Immunological challenges for peptide-based immunotherapy in glioblastoma

Mohme

Neidert

Regli

et al. 2014

Cancer Treatment Reviews

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Glioblastoma is the most aggressive primary tumor of the central nervous system with a medium overall survival of 7-15months after diagnosis. Since tumor cells penetrate the surrounding brain tissue, complete surgical resection is impossible and tumor recurrence is almost a certainty. New treatment modalities are therefore needed, and these should be able to trace, identify, and kill dispersed tumor cells with great accuracy. Immunological approaches in principle meet these needs. Unfortunately, due to profound tumor-associated mechanisms of immunosuppression and -evasion, immunotherapeutic strategies like peptide vaccination have so far not been translated into clinical success. If future, peptidebased vaccination approaches shall be successful in glioblastoma therapy, multiple questions need to be solved including identification of suitable antigens, route and mode of vaccination, preparation of the tumor-bearing "host" and antagonizing, as much as this is possible, glioblastoma-associated mechanisms of immune evasion and poor vaccination response. In this review we will address the immunological challenges of glioblastoma and discuss key aspects that have rendered successful immunotherapy difficult in the past. preparation of the tumor-bearing "host" and antagonizing, as much as this is possible, glioblastoma-associated mechanisms of immune evasion and poor vaccination response. In this review we will address the immunological challenges of glioblastoma and discuss key aspects that have rendered successful immunotherapy difficult in the past.

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Section: 87mentioning

confidence: 99%

Immunological challenges for peptide-based immunotherapy in glioblastoma

Mohme

Neidert

Regli

et al. 2014

Cancer Treatment Reviews

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“…The tumor progression is significantly delayed in mice harboring vitiligo compared with mice without depigmented skin (14). The development of vitiligo in melanoma patients has also been associated with a better prognosis (15)(16)(17)(18). It occurs most often in immunotherapeutic trials, although vitiligo may also develop in patients treated with surgery, radiotherapy, or chemotherapy.…”

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confidence: 99%

Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4⁺T cells

Pommier

Audemard

Durand

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ ret mice develop cutaneous metastases and, finally, distant metastases. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression. Here, we find that regulatory CD4 + T cells accumulate in the skin, the spleen, and tumor-draining lymph nodes of MT/ret mice not developing vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the skin of MT/ret mice with active vitiligo. Moreover, they inhibit tumor cell proliferation in vitro through a reactive oxygen species-dependent mechanism, and both their depletion and reactive oxygen species neutralization in vivo increased tumor cell dissemination. Altogether, our data suggest that regulatory CD4 + T cells favor tumor progression, in part, by inhibiting recruitment and/or differentiation of inflammatory monocytes in the skin.T he concept of suppressive T cells, which was first described in the early 1970s, remained poorly investigated until Sakaguchi et al. demonstrated the suppressive functions of a subset of CD4 + T cells now called regulatory T cells (Tregs) (1). Tregs express Foxp3 (2) and high surface levels of the α-chain of the IL-2 receptor (CD25) and are the main mediators of peripheral tolerance under physiological settings (1). Their role in the suppression of antitumor immunity was originally described in the 1980s (3) but remained, at first, largely underestimated. The demonstration that systemic depletion of Tregs favors tumor rejection in mouse models highlighted their contribution in tumor progression (4). Whereas it is established that Tregs potently interfere with tumorspecific T cells (5-8), their impact on innate immune cells, in particular, on myeloid cells, has been clearly less investigated in the context of tumor development (9, 10).To decipher the role of Tregs in the relationship between cancer immunity and autoimmunity, we used mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice) (11). In this model, the primary uveal tumor disseminates early but remains dormant for several weeks (12, 13). MT/ret mice then develop cutaneous metastases and finally distant (i.e., pulmonary, visceral, and mediastinal adenopathy) metastases (14). A significant proportion of MT/ret mice spontaneously develops vitiligo-like depigmentations. The tumor progression is significantly delayed in mice harboring vitiligo compared with mice without depigmented skin (14). The development of vitiligo in melanoma patients has...

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“…IL-2 has many effects on the immune system including, but not limited to, playing a vital role in allowing cells to discriminate between "self" and "non-self" antigens (8). In a normal immune response, CD4 + T cells are presented an antigen; if the CD4 + T cell recognizes the antigen, the cell becomes activated and IL-2 is released (8).…”

Section: Discussionmentioning

confidence: 99%

“…In a normal immune response, CD4 + T cells are presented an antigen; if the CD4 + T cell recognizes the antigen, the cell becomes activated and IL-2 is released (8). IL-2 has a positive feedback on the CD4 + T cell resulting in immunologic memory, as well as recruiting other immune cells including CD8 + T cells, also known as cytotoxic T lymphocytes (CTLs) (8) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy-induced Leukoderma from Treatment of Melanoma with IL-2: A Case Report and a Review of the Literature

Gathings¹,

Lewallen²,

Yosipovitch³

2015

Acta Derm Venerol

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Melanoma-associated leukoderma (MAL) is a relatively uncommon phenomenon in the literature that can present (1) before melanoma detection, (2) after detection and before treatment, and (3) after treatment with immunotherapeutic agents. We report a case of MAL in an 83-year-old man after treatment with high dose IL-2 for metastatic melanoma and further describe the literature of the underlying mechanisms behind it that involve the immune system. Cytotoxic CD8+ T cells are thought the mediate the process at a cellular level. Self-antigens (e.g. MART-1/2, gp100, tyrosinase) have been presented on the surface of both normal and malignant melanocytes and mediate the development of MAL after cytotoxic CD8+ T cells attack both cell types. Autoimmune manifestations have a positive effect on tumor immunity, with patients at stage III and stage IV melanoma showing a better prognosis after leukoderma development. In addition, immunotherapy induced leukoderma has been associated with a higher therapeutic response rate. Recently, newer immuno-therapeutic drugs, such as vemurafenib and ipilimumab, have been associated with leukoderma as a side effect.

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New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

Cited by 91 publications

References 85 publications

Immunological challenges for peptide-based immunotherapy in glioblastoma

Immunological challenges for peptide-based immunotherapy in glioblastoma

Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4⁺T cells

Immunotherapy-induced Leukoderma from Treatment of Melanoma with IL-2: A Case Report and a Review of the Literature

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New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

Cited by 91 publications

References 85 publications

Immunological challenges for peptide-based immunotherapy in glioblastoma

Immunological challenges for peptide-based immunotherapy in glioblastoma

Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4+T cells

Immunotherapy-induced Leukoderma from Treatment of Melanoma with IL-2: A Case Report and a Review of the Literature

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Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4⁺T cells