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Novel Developments on Skin Cancer Diagnostics and Treatment

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 10 August 2024 | Viewed by 6303

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Special Issue Editor

Prof. Dr. Christoffer Gebhardt

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Guest Editor

1. Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany
2. Fleur Hiege Center für Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany
Interests: immuno-oncology; melanoma; cutaneous squamous cell carcinoma; uveal melanoma; liquid biopsy; circulating tumor-derived DNA; molecular diagnostics; gene expression profiling; proteomics; damage-associated molecular pattern; innate immunity; tumor micro-environment

Special Issue Information

Dear Colleagues,

Skin cancer treatment has advanced tremendously with novel immunotherapies and targeted therapies significantly improving patients' survival. Most interestingly, skin cancers, such as melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma and others, share a similar pathogenesis as exposure to sunlight is considered the main risk factor for genetic mutations and the subsequent malignant transformation. Nevertheless, there is still a relatively high risk for treatment resistance and severe treatment-related side effects. In order to identify patients at risk, to select the best treatment regime and sequence, and to predict treatment-related toxicity, molecular diagnostics are needed based on a deep understanding of the complex underlying mechanisms. In this Special Issue, we will publish original research articles and reviews providing new insights into skin cancer diagnostics and treatment.

We look forward to receiving your contributions.

Prof. Dr. Christoffer Gebhardt
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

melanoma
cutaneous squamous cell carcinoma
uveal melanoma
basal cell carcinoma
Merkel cell carcinoma
liquid biopsy
molecular diagnostics
immune checkpoint inhibition
immune cell subsets
treatment resistance

Published Papers (4 papers)

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Research

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14 pages, 1361 KiB

Open AccessArticle

High Serum Levels of CCL20 Are Associated with Recurrence and Unfavorable Overall Survival in Advanced Melanoma Patients Receiving Immunotherapy

by Julian Kött, Inka Lilott Hoehne, Isabel Heidrich, Noah Zimmermann, Kim-Lea Reese, Tim Zell, Glenn Geidel, Alessandra Rünger, Stefan W. Schneider, Klaus Pantel, Daniel J. Smit and Christoffer Gebhardt

Cancers 2024, 16(9), 1737; https://doi.org/10.3390/cancers16091737 - 29 Apr 2024

Viewed by 604

Abstract

Background: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. Methods: In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes. Results: An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2–6 months) vs. 11 months (95% CI: 6–26 months)) (p = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25–3.12, p = 0.004) and multivariate (HR: 1.99, 95% CI 1.21–3.29, p = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, p = 0.042) with an HR of 1.85 (95% CI 1.02–3.37, p = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02–3.88, p = 0.043). Conclusions: CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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15 pages, 2304 KiB

Open AccessArticle

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study

by Barbara Bailly-Caillé, Diane Kottler, Rémy Morello, Marie Lecornu, William Kao, Emmanuel Meyer, Anne Dompmartin and Jean-Matthieu L’Orphelin

Cancers 2023, 15(2), 495; https://doi.org/10.3390/cancers15020495 - 13 Jan 2023

Cited by 9 | Viewed by 2074

Abstract

Background: Cemiplimab is a monoclonal antibody targeting the PD-1, and phase II trials have shown its efficacy in the treatment of advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy as a first- or later-line treatment. A synergistic antitumoral response has been demonstrated with concurrent radiotherapy and PD1-immunotherapy. However, no real-life study has demonstrated this effect in advanced cutaneous squamous cell carcinoma. Methods: We conducted a real-life retrospective cohort study to investigate the benefit of concomitant therapy in 33 patients treated with cemiplimab at the University Hospital of Caen, alone (C group) or concomitant to radiotherapy (C/RT group). Our primary objectives were to evaluate the best overall response and objective response rate. Our secondary objectives were the disease control rate, median time to response, progression-free survival, overall survival, clinical benefit of radiotherapy, and safety data. After stopping cemiplimab administration, we performed a follow-up of our patients and performed a descriptive study. Results: We reported an objective response rate of 45.5%, including 47.6% in the cemiplimab group versus 41.6% in the concomitant group. The addition of radiotherapy to cemiplimab enables an earlier clinico-radiological response, with a median duration of 5.5 months in the cemiplimab group versus 3 months in the concomitant therapy group. The response to treatment was prolonged despite discontinuation of cemiplimab, with 91.6% (n = 11/12) and 83.3% (n = 10/12) patients in complete or partial remission at 6 months and 1 year after cessation of cemiplimab and no switch to another oncological treatment, respectively. Radiation therapy also provided a therapeutic effect in 83.3% of the patients in the concomitant group, without increasing the occurrence of adverse events. Conclusions: Our study confirms the efficacy of cemiplimab and radiotherapy in the management of advanced cutaneous squamous cell carcinoma. Concomitant therapy permitted to obtain an earlier radiological response, a beneficial local therapeutic effect of radiotherapy, without any safety alert. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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19 pages, 7923 KiB

Open AccessArticle

Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma

by Nadine L. Ammann, Yasmin F. Schwietzer, Christian Mess, Julia-Christina Stadler, Glenn Geidel, Julian Kött, Klaus Pantel, Stefan W. Schneider, Jochen Utikal, Alexander T. Bauer and Christoffer Gebhardt

Cancers 2022, 14(22), 5676; https://doi.org/10.3390/cancers14225676 - 18 Nov 2022

Cited by 4 | Viewed by 1753

Abstract

Immune checkpoint inhibition (ICI) has yielded remarkable results in prolonging survival of metastatic melanoma patients but only a subset of individuals treated respond to therapy. Success of ICI treatment appears to depend on the number of tumor-infiltrating effector T-cells, which are known to be influenced by activated eosinophils. To verify the co-occurrence of activated eosinophils and T-cells in melanoma, immunofluorescence was performed in 285 primary or metastatic tumor tissue specimens from 118 patients. Moreover, eosinophil counts and activity markers such as eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) were measured in the serum before therapy start and before the 4th infusion of ICI in 45 metastatic unresected melanoma patients. We observed a positive correlation between increased tumor-infiltrating eosinophils and T-cells associated with delayed melanoma progression. High baseline levels of eosinophil count, serum ECP and EPX were linked to prolonged progression-free survival in metastatic melanoma. Our data provide first indications that activated eosinophils are related to the T-cell-inflamed tumor microenvironment and could be considered as potential future prognostic biomarkers in melanoma. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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Review

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22 pages, 1512 KiB

Open AccessReview

Medical Needs and Therapeutic Options for Melanoma Patients Resistant to Anti-PD-1-Directed Immune Checkpoint Inhibition

by Jessica C. Hassel, Lisa Zimmer, Thomas Sickmann, Thomas K. Eigentler, Friedegund Meier, Peter Mohr, Tobias Pukrop, Alexander Roesch, Dirk Vordermark, Christina Wendl and Ralf Gutzmer

Cancers 2023, 15(13), 3448; https://doi.org/10.3390/cancers15133448 - 30 Jun 2023

Cited by 1 | Viewed by 1307

Abstract

Available 4- and 5-year updates for progression-free and for overall survival demonstrate a lasting clinical benefit for melanoma patients receiving anti-PD-directed immune checkpoint inhibitor therapy. However, at least one-half of the patients either do not respond to therapy or relapse early or late following the initial response to therapy. Little is known about the reasons for primary and/or secondary resistance to immunotherapy and the patterns of relapse. This review, prepared by an interdisciplinary expert panel, describes the assessment of the response and classification of resistance to PD-1 therapy, briefly summarizes the potential mechanisms of resistance, and analyzes the medical needs of and therapeutic options for melanoma patients resistant to immune checkpoint inhibitors. We appraised clinical data from trials in the metastatic, adjuvant and neo-adjuvant settings to tabulate frequencies of resistance. For these three settings, the role of predictive biomarkers for resistance is critically discussed, as well as are multimodal therapeutic options or novel immunotherapeutic approaches which may help patients overcome resistance to immune checkpoint therapy. The lack of suitable biomarkers and the currently modest outcomes of novel therapeutic regimens for overcoming resistance, most of them with a PD-1 backbone, support our recommendation to include as many patients as possible in novel or ongoing clinical trials. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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