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Molecular Basis and Progress of Immunotherapy for Melanoma
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Molecular Basis and Progress of Immunotherapy for Melanoma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 6196

Special Issue Editor

Dr. George Ansstas

E-Mail Website
Guest Editor
Division of Medical Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO 63130, USA
Interests: genetic and epigenetic; glioblastoma; melanoma; tumor microenvironment

Special Issue Information

Dear Colleagues,

The treatment landscape of melanoma is evolving beyond BRAF-targeted therapy and immune checkpoint inhibitors. Our improved understanding of cell survival pathways, chromatin remodeling, and DNA damage repair have led to major and critical observations that will lead to more targeted treatments based on individual tumor needs. Also, the field of immune therapies is expanding to more immune checkpoint inhibitors, cellular therapies (unmodified and modified), and bi-specific T cell engagers.

In this Special Issue, we will focus on the critical findings from basic, translational, and early clinical data that will hold promise in expanding our vision in this rapidly evolving field. Since IJMS is a journal of molecular science, pure clinical or model studies will not be suitable for our journal. However, clinical or pure model submissions with biomolecular experiments are welcomed.

Dr. George Ansstas
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • immune checkpoint inhibitors
  • immune therapies
  • T cell
  • NK cells

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Published Papers (3 papers)

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Review

42 pages, 2925 KiB  
Review
Detection of Circulating Tumor DNA in Liquid Biopsy: Current Techniques and Potential Applications in Melanoma
by Clara Martínez-Vila, Cristina Teixido, Francisco Aya, Roberto Martín, Europa Azucena González-Navarro, Llucia Alos, Natalia Castrejon and Ana Arance
Int. J. Mol. Sci. 2025, 26(2), 861; https://doi.org/10.3390/ijms26020861 - 20 Jan 2025
Cited by 1 | Viewed by 1855
Abstract
The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting BRAFV600 mutations, as well as immune checkpoint inhibitors (ICI) like anti-PD-1 monotherapy or its combinations with anti-CTLA-4 or anti-LAG-3. Despite that, many patients [...] Read more.
The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting BRAFV600 mutations, as well as immune checkpoint inhibitors (ICI) like anti-PD-1 monotherapy or its combinations with anti-CTLA-4 or anti-LAG-3. Despite that, many patients still do not benefit from these treatments at all or develop resistance mechanisms. Therefore, prognostic and predictive biomarkers are needed to identify patients who should switch or escalate their treatment strategies or initiate an intensive follow-up. In melanoma, liquid biopsy has shown promising results, with a potential role in predicting relapse in resected high-risk patients or in disease monitoring during the treatment of advanced disease. Several components in peripheral blood have been analyzed, such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulant tumoral DNA (ctDNA), which have turned out to be particularly promising. To analyze ctDNA in blood, different techniques have proven to be useful, including digital droplet polymerase chain reaction (ddPCR) to detect specific mutations and, more recently, next-generation sequencing (NGS) techniques, which allow analyzing a broader repertoire of the mutation landscape of each patient. In this review, our goal is to update the current understanding of liquid biopsy, focusing on the use of ctDNA as a biological material in the daily clinical management of melanoma patients, in particular those with advanced disease treated with ICI. Full article
(This article belongs to the Special Issue Molecular Basis and Progress of Immunotherapy for Melanoma)
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18 pages, 299 KiB  
Review
Recent Advancements in Cell-Based Therapies in Melanoma
by George Nassief, Angela Anaeme, Karen Moussa, Abdallah N. Mansour and George Ansstas
Int. J. Mol. Sci. 2024, 25(18), 9848; https://doi.org/10.3390/ijms25189848 - 12 Sep 2024
Cited by 1 | Viewed by 1976
Abstract
Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that [...] Read more.
Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. In the realm of cancer therapy, cell-based therapies utilize immune cells to target tumor cells while sparing healthy cells. Recently, the Food and Drug Administration (FDA) has approved the usage of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced melanoma. This came following recent results from the C-144-01 study (NCT02360579), which demonstrated the efficacy and safety of TILs in metastatic melanoma patients who otherwise failed on standard ICI/targeted therapy. Thus, the results of this trial as well as the recent FDA approval have proven the viability of utilizing cell-based therapies to fill the gap in treatment options for patients with advanced melanoma. This review aims to provide a comprehensive overview of major cell-based therapies that have been utilized in melanoma by delineating results of the most recent multi-center phase II/ III clinical trials that evaluate the efficacy and safety of major cell-based therapies in melanoma. Additionally, we provide a summary of current limitations in each cell-based therapeutic option as well as a future direction of how to further extrapolate these cell-based therapies in advanced melanoma. Full article
(This article belongs to the Special Issue Molecular Basis and Progress of Immunotherapy for Melanoma)
27 pages, 2032 KiB  
Review
Lymphocyte T Subsets and Outcome of Immune Checkpoint Inhibitors in Melanoma Patients: An Oncologist’s Perspective on Current Knowledge
by Clara Martínez-Vila, Europa Azucena González-Navarro, Cristina Teixido, Roberto Martin, Francisco Aya, Manel Juan and Ana Arance
Int. J. Mol. Sci. 2024, 25(17), 9506; https://doi.org/10.3390/ijms25179506 - 31 Aug 2024
Cited by 1 | Viewed by 1975
Abstract
Melanoma is the most aggressive and deadly form of skin cancer, and its incidence has been steadily increasing over the past few decades, particularly in the Caucasian population. Immune checkpoint inhibitors (ICI), anti-PD-1 monotherapy or in combination with anti-CTLA-4, and more recently, anti-PD-1 [...] Read more.
Melanoma is the most aggressive and deadly form of skin cancer, and its incidence has been steadily increasing over the past few decades, particularly in the Caucasian population. Immune checkpoint inhibitors (ICI), anti-PD-1 monotherapy or in combination with anti-CTLA-4, and more recently, anti-PD-1 plus anti-LAG-3 have changed the clinical evolution of this disease. However, a significant percentage of patients do not benefit from these therapies. Therefore, to improve patient selection, it is imperative to look for novel biomarkers. Immune subsets, particularly the quantification of lymphocyte T populations, could contribute to the identification of ICI responders. The main purpose of this review is to thoroughly examine significant published data on the potential role of lymphocyte T subset distribution in peripheral blood (PB) or intratumorally as prognostic and predictive of response biomarkers in advanced melanoma patients treated with ICI regardless of BRAFV600 mutational status. Full article
(This article belongs to the Special Issue Molecular Basis and Progress of Immunotherapy for Melanoma)
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