Tumor Microenvironment and Melanoma Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 3663

Special Issue Editors


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Guest Editor
Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80131 Napoli, Italy
Interests: melanoma biomarkers; immunotherapy response; clinical studies

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Guest Editor
Pathology Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, Italy
Interests: Immunohistochemistry; melanoma research; digital pathology

E-Mail Website
Guest Editor
Pathology Unit, Istituto Nazionale Tumori-Irccs-Fondazione G. Pascale, 80131 Naples, Italy
Interests: molecular diagnostics; melanoma research; biobanking

Special Issue Information

Dear Colleagues,

The tumor microenvironment mainly represented by the lymphocyte infiltrate (TIL), macrophages, mast cells, neutrophils and dendritic cells, the main protagonists of the inflammatory process, plays a fundamental role in neoplastic evolution and in the modulation of the response of anti-tumor drugs. In many types of cancer, the presence of TIL has been correlated with a favorable prognosis. Immunotherapy has therefore become an important part of the treatment of certain types of cancer in recent decades, especially for advanced melanoma. The evaluation of the expression of PD-L1 on tumor cells and/or immune cells is the most investigated biomarker, even if its predictive value is much discussed. Instead, the definition of the complex profile of immune cells (immunoprofiling) in the tumor microenvironment has taken on an increasingly important prognostic/predictive value. Different lymphocyte subgroups can activate or inhibit the immune response. In particular, regulatory T cells (FOXP3) and TAM, "tumor-associated macrophages" (CD163 +), have an inhibitory effect on the immune response mediated by active cytotoxic T lymphocytes (TCL) (CD8 + / GRZB +) and natural killer cells (CD57 +). The balance of these entities as well as the concomitant expression of other immune-checkpoint molecules could provide information for the prediction of the response to immunotherapies.

The aim of this Special Issue will be to present the description and identification of new molecular targets linked to the tumor microenvironment and the availability of modern immunotherapeutic approaches capable of improving the treatment of advanced melanoma.

Dr. Mariaelena Capone
Dr. Giosue Scognamiglio
Dr. Margherita Cerrone
Guest Editors

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Keywords

  • TME biomarkers
  • advanced melanoma
  • immunotherapy
  • molecular target
  • tumor microenvironment

Published Papers (2 papers)

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Review

16 pages, 3534 KiB  
Review
In Vitro Three-Dimensional (3D) Models for Melanoma Immunotherapy
by Gemma Nomdedeu-Sancho, Anastasiya Gorkun, Naresh Mahajan, Kelsey Willson, Cecilia R. Schaaf, Konstantinos I. Votanopoulos, Anthony Atala and Shay Soker
Cancers 2023, 15(24), 5779; https://doi.org/10.3390/cancers15245779 - 09 Dec 2023
Viewed by 1432
Abstract
Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may [...] Read more.
Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may develop resistance over time. Tumor growth and its response to therapies are critically influenced by the tumor microenvironment (TME); it directly supports cancer cell growth and influences the behavior of surrounding immune cells, which can become tumor-permissive, thereby rendering immunotherapies ineffective. Ex vivo modeling of melanomas and their response to treatment could significantly advance our understanding and predictions of therapy outcomes. Efforts have been directed toward developing reliable models that accurately mimic melanoma in its appropriate tissue environment, including tumor organoids, bioprinted tissue constructs, and microfluidic devices. However, incorporating and modeling the melanoma TME and immune component remains a significant challenge. Here, we review recent literature regarding the generation of in vitro 3D models of normal skin and melanoma and the approaches used to incorporate the immune compartment in such models. We discuss how these constructs could be combined and used to test immunotherapies and elucidate treatment resistance mechanisms. The development of 3D in vitro melanoma models that faithfully replicate the complexity of the TME and its interaction with the immune system will provide us with the technical tools to better understand ICI resistance and increase its efficacy, thereby improving personalized melanoma therapy. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Melanoma Therapy)
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18 pages, 1323 KiB  
Review
Helper Innate Lymphoid Cells—Unappreciated Players in Melanoma Therapy
by Cinzia Garofalo, Annamaria Cerantonio, Carolina Muscoli, Vincenzo Mollace, Giuseppe Viglietto, Carmela De Marco and Costanza Maria Cristiani
Cancers 2023, 15(3), 933; https://doi.org/10.3390/cancers15030933 - 01 Feb 2023
Cited by 1 | Viewed by 1532
Abstract
Immune checkpoint inhibitors (ICIs) and targeted therapy have dramatically changed the outcome of metastatic melanoma patients. Although immune checkpoints were developed based on the biology of adaptive T cells, they have subsequently been shown to be expressed by other subsets of immune cells. [...] Read more.
Immune checkpoint inhibitors (ICIs) and targeted therapy have dramatically changed the outcome of metastatic melanoma patients. Although immune checkpoints were developed based on the biology of adaptive T cells, they have subsequently been shown to be expressed by other subsets of immune cells. Similarly, the immunomodulatory properties of targeted therapy have been studied primarily with respect to T lymphocytes, but other subsets of immune cells could be affected. Innate lymphoid cells (ILCs) are considered the innate counterpart of T lymphocytes and include cytotoxic natural killer cells, as well as three helper subsets, ILC1, ILC2 and ILC3. Thanks to their tissue distribution and their ability to respond rapidly to environmental stimuli, ILCs play a central role in shaping immunity. While the role of NK cells in melanoma physiopathology and therapy is well established, little is known about the other helper ILC subsets. In this review, we summarize recent findings on the ability of the melanoma TME to influence the phenotype and functional plasticity of helper ILCs and highlight how this subset may in turn shape the TME. We also discuss changes in the melanoma TME induced by targeted therapy that could affect helper ILC functions, the expression of immune checkpoints on this subset and how their inhibition by ICIs may modulate helper ILC function and contribute to therapeutic efficacy. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Melanoma Therapy)
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