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Cancers
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Immune Checkpoint Inhibitors in Cutaneous Oncology
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Immune Checkpoint Inhibitors in Cutaneous Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 6540

Special Issue Editor

Dr. Joseph Markowitz

E-Mail Website
Guest Editor
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Interests: melanoma; checkpoint resistance; immunotherapy; translational informatics; nitric oxide; multiomics; melanoma therapy

Special Issue Information

Dear Colleagues,

Checkpoint inhibitors are widely used in cutaneous malignancies. These cancers include, but are not limited to, melanoma of cutaneous origin, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. In the last 10 years, the prognosis of these cancers has improved due to the introduction of checkpoint blockades into the clinic. The current FDA-approved agents are monoclonal antibodies that are directed against the checkpoint molecules on the surface of immune or cancer cells (e.g., PD-1, PD-L1, CTLA-4, and LAG-3).

However, even with these advances, many patients do not respond to these therapeutic approaches. In addition, there are many immune-related toxicities that make these agents problematic. The goal of this Special Issue is to develop a clinical summary of the current state-of-the-art treatments for cutaneous malignancies that involve checkpoint blockades, discuss immune-mediated reactions to checkpoint inhibition, and begin to understand the key mechanisms of current checkpoint blockade inhibition identified in laboratory studies to mitigate resistance. Clinical or translational informatics papers that describe how these agents can be delivered efficiently in the clinic or which describe new pipelines that elucidate new therapeutic approaches for enhancing checkpoint blockade efficacy in cutaneous malignancies are also welcome.

Dr. Joseph Markowitz
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
  • Merkel cell carcinoma
  • checkpoint blockade
  • immune-related adverse events
  • resistance to checkpoint blockade
  • PD-1
  • PD-L1
  • CTLA-4
  • LAG-3

Published Papers (3 papers)

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Research

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11 pages, 1185 KiB  
Article
Dichotomous Nitric Oxide–Dependent Post-Translational Modifications of STAT1 Are Associated with Ipilimumab Benefits in Melanoma
by Saurabh K. Garg, James Sun, Youngchul Kim, Junmin Whiting, Amod Sarnaik, José R. Conejo-Garcia, Mitch Phelps, Jeffrey S. Weber, James J. Mulé and Joseph Markowitz
Cancers 2023, 15(6), 1755; https://doi.org/10.3390/cancers15061755 - 14 Mar 2023
Cited by 1 | Viewed by 1442
Abstract
Although Ipilimumab (anti-CTLA-4) is FDA-approved for stage III/IV melanoma adjuvant treatment, it is not used clinically in first-line therapy, given the superior relapse-free survival (RFS)/toxicity benefits of anti-PD-1 therapy. However, it is important to understand anti-CTLA-4’s mechanistic contribution to combination anti-PD-1/CTLA-4 therapy and [...] Read more.
Although Ipilimumab (anti-CTLA-4) is FDA-approved for stage III/IV melanoma adjuvant treatment, it is not used clinically in first-line therapy, given the superior relapse-free survival (RFS)/toxicity benefits of anti-PD-1 therapy. However, it is important to understand anti-CTLA-4’s mechanistic contribution to combination anti-PD-1/CTLA-4 therapy and investigate anti-CTLA-4 therapy for BRAF-wild type melanoma cases reresected after previous adjuvant anti-PD-1 therapy. Our group published that nitric oxide (NO) increased within the immune effector cells among patients with longer RFS after adjuvant ipilimumab, whereas NO increased within the immune suppressor cells among patients with shorter RFS. Herein, we measured the post-translational modifications of STAT1 (nitration-nSTAT1 and phosphorylation-pSTAT1) that are important for regulating its activity via flow cytometry and mass spectrometry approaches. PBMCs were analyzed from 35 patients undergoing adjuvant ipilimumab treatment. Shorter RFS was associated with higher pSTAT1 levels before (p = 0.007) and after (p = 0.036) ipilimumab. Ipilimumab-treated patients with high nSTAT1 levels before and after therapy in PBMCs experienced decreased RFS, but the change in nSTAT1 levels before and after ipilimumab therapy was associated with longer RFS (p = 0.01). The measurement of post-translational modifications in STAT1 may distinguish patients with prolonged RFS from ipilimumab and provide mechanistic insight into responses to ipilimumab combination regimens. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors in Cutaneous Oncology)
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Review

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18 pages, 2623 KiB  
Review
Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field
by Islam Eljilany, Ella Castellano and Ahmad A. Tarhini
Cancers 2023, 15(16), 4125; https://doi.org/10.3390/cancers15164125 - 16 Aug 2023
Cited by 2 | Viewed by 1973
Abstract
The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose [...] Read more.
The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials. In contemporary clinical practice, the adjuvant treatment approach for surgically resected stage III-IV melanoma has undergone a notable shift towards the utilization of nivolumab, pembrolizumab, and BRAF-MEK inhibitors, such as dabrafenib plus trametinib (specifically for BRAF mutant melanoma) due to the significant enhancements in RFS observed with these treatments. Pembrolizumab has obtained regulatory approval in the United States to treat resected stage IIB-IIC melanoma, while nivolumab is currently under review for the same indication. This review comprehensively analyzes completed phase III adjuvant therapy trials in adjuvant therapy. Additionally, it provides a summary of ongoing trials and an overview of the main challenges and future directions with adjuvant therapy. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors in Cutaneous Oncology)
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18 pages, 699 KiB  
Review
Dietary Considerations for Inflammatory Bowel Disease Are Useful for Treatment of Checkpoint Inhibitor-Induced Colitis
by Aditi Saha, Isabella Dreyfuss, Humaira Sarfraz, Mark Friedman and Joseph Markowitz
Cancers 2023, 15(1), 84; https://doi.org/10.3390/cancers15010084 - 23 Dec 2022
Cited by 2 | Viewed by 2481
Abstract
Checkpoint molecules are cell surface receptors on immune cells that mitigate excessive immune responses, but they have increased expression levels in cancer to facilitate immune escape. Checkpoint blockade therapies (e.g., anti–PD-1, anti–CTLA-4, and anti–LAG-3 therapy, among others) have been developed for multiple cancers. [...] Read more.
Checkpoint molecules are cell surface receptors on immune cells that mitigate excessive immune responses, but they have increased expression levels in cancer to facilitate immune escape. Checkpoint blockade therapies (e.g., anti–PD-1, anti–CTLA-4, and anti–LAG-3 therapy, among others) have been developed for multiple cancers. Colitis associated with checkpoint blockade therapy has pathophysiological similarities to inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis. Current therapeutic guidelines for checkpoint blockade-induced colitis include corticosteroids and, if the patient is refractory to steroids, immunomodulating antibodies, such as anti-TNF and anti-integrin agents. Interestingly, immunomodulatory molecules, such as TNFα, are upregulated in both IBD and checkpoint-mediated colitis. The inflammatory colitis toxicity symptoms from checkpoint blockade are similar to clinical symptoms experienced by patients with IBD. The pathophysiologic, dietary, and genetic factors associated with IBD will be reviewed. We will then explain how the principles developed for the treatment of IBD can be applied to patients experiencing inflammatory bowel toxicity secondary to checkpoint blockade. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors in Cutaneous Oncology)
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