Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review

Immune checkpoint inhibitors (ICIs), which target CTLA-4 or PD-(L)1 molecules, have shown impressive therapeutic results. Durable responses, however, are only observed in a segment of the patient population and must be offset against severe off-target immune toxicity and high costs. This calls for biomarkers that predict response during ICI treatment. Although many candidate biomarkers exist, as yet, there has been no systematic overview of biomarkers predictive during. Here, we provide a systematic review of the current literature of ICI treatment to establish an overview of candidate predictive biomarkers during ICI treatment in melanoma patients. We performed a systematic Medline search (2000–2018, 1 January) on biomarkers for survival or response to ICI treatment in melanoma patients. We retrieved 735 publications, of which 79 were finally included in this systematic review. Blood markers were largely studied for CTLA-4 ICI, whereas tumor tissue markers were analyzed for PD-(L)1 ICI. Blood cytology and soluble factors were more frequently correlated to overall survival (OS) than response, indicating their prognostic rather than predictive nature. An increase in tumor-infiltrating CD8 + T-cells and a decrease in regulatory T-cells were correlated to response, in addition to mutational load, neoantigen load, and immune-related gene expression. Immune-related adverse events were also associated frequently with a favorable response and OS. This review shows the great va...
Source: Melanoma Research - Category: Cancer & Oncology Tags: Review Article Source Type: research

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Abstract Current therapies for metastatic melanoma (anti-PD1 and BRAF/MEK inhibitors) can cause drug-induced vitiligo. The aim of this study is to dermatologically define and histologically characterize this new type of vitiligo, and assess the clinical course of the disease. Fourteen patients with metastatic melanoma treated with immune or targeted therapy were included in a dataset evaluating clinical data, vitiligo description and histopathological features. Vitiligo-like lesions occurred after a mean of 7.5 months from the start of the therapies (range 1-42 months), with a prevalence of the non-segmental varia...
Source: Acta Derm Venereol A... - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research
We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital ...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research
ConclusionsImmunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
This article presents the case of a 68-year-old female patient who reported bilateral progressive visual loss over 4 weeks. The patient had a known metastatic malignant cutaneous melanoma, which was treated with the immune checkpoint inhibitors nivolumab and ipilimumab. The ophthalmological examination revealed a bilateral anterior chamber flare with endothelial precipitates as well as choroidal folds, an orange-red discoloration of the retina and a serous retinal/choroidal detachment in the left eye. In the course of time the patient developed poliosis and vitiligo. Systemic and local steroid treatment...
Source: Der Ophthalmologe - Category: Opthalmology Authors: Tags: Ophthalmologe Source Type: research
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a Type I transmembrane glycoprotein which has important roles in cancer and amyotrophic lateral sclerosis (ALS). In skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in pigmentation. Previously, we showed that GPNMB was highly expressed in keratinocytes from healthy donors, but decreased in vitiligo lesions. The function of keratinocyte-derived GPNMB is yet to be known. Therefore, we first confirmed GPNMB expression in cultured normal human epidermal keratinocytes, and oxidative stress (H2O2) down-regulated both membrane GPNMB and so...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Photobiology and Pigmentation Source Type: research
Narrow-band ultraviolet B (NBUVB) phototherapy has been the mainstay in treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. We performed a nationwide population-based retrospective cohort study to investigate the risks of actinic keratosis (AK), Bowen ’s disease (BD), nonmelanoma skin cancers (NMSC), and melanoma, based on the number of NBUVB phototherapy sessions of patients with vitiligo. We obtained cohort data from the Korean National Health Insurance Claims database for the period January 2007 to December 2017.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Clinical Research and Epidemiology Source Type: research
The objective of this study was to investigate the role of CLEC12B in melanoma. Expression of CLEC12B was assessed in melanoma cell lines, nevi and melanoma samples. Using a lentivirus construct we overexpressed (Ov) or downregulated (Sh) CLEC12B in melanoma cells lines to assess the effect of its modulation on proliferation and cell cycle. The signaling pathway involved was then studied.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research
Nivolumab, a checkpoint inhibitor of programmed cell death receptor-1 (PD-1), is used in the treatment of metastatic melanoma and nonsmall cell lung cancer. Blockade of PD-1 receptor releases inhibition of T-cell activation and allows for an antitumor immune response. As with many immune-mediated therapeutics, the most common cutaneous immune-related adverse events reported in association with nivolumab are vitiligo, rash and pruritis. Other autoimmune and inflammatory skin conditions such as psoriasiform or lichenoid eruptions, autoimmune blistering disorders, and sarcoidosis have also been reported.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
We report a 59-year-old who presented with a BRAF-wild type primary melanoma on the left shoulder.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
Background: Dermatological toxicities (lichenoid, immune-bullous, vitiligo, acantholytic, granulomatous, panniculitis etc.) to programmed cell death receptor 1 (PD-1) inhibition are reported in 30-40% of patients. Here we present a patient with sarcoidal granulomas and septal panniculitis on pembrolizumab.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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