Extracellular adenosine metabolism in immune cells in melanoma

Abstract Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, which leads to a strong immunosuppression associated with a rapid tumor progression. Adenosine is considered as one of the main immunosuppressive factors in the tumor environment. It is produced via enzymatic hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 localized on cell surface. Using the ret transgenic mouse melanoma model that closely mimics human melanoma, we demonstrated an increased frequency of ectonucleotidase-positive myeloid-derived suppressor cells (MDSCs) in melanoma lesions and lymphoid organs. Furthermore, we observed that conventional CD4+FoxP3− and CD8+ T cells infiltrating melanoma lesions of ret transgenic mice were distinctly enriched in the CD39+CD73+ subpopulation that co-expressed also PD-1. Ectonucleotidase expression was also up-regulated in CD4+ and CD8+ T cells upon activation. In addition, these ectoenzymes were largely found to be expressed on memory T cell compartment (in particular, on effector memory cells). Our data suggest that extracellular adenosine produced by regulatory T cells (Tregs) and MDSCs can suppress T cell effector functions through paracrine signaling. Another mechanism involves its production also by effector T cells and an inhibition of their anti-tumor reactivity via autocrine signaling as a part of the negative feedback loop. This mode of adenosine signaling could be also...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Conditions:   Melanoma Stage III;   Melanoma Stage IV;   Inoperable Disease Interventions:   Drug: Interleukin-2;   Drug: Ipilimumab;   Drug: Nivolumab Sponsors:   H. Lee Moffitt Cancer Center and Research Institute;   Clinigen Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
AbstractWhen detected early, melanoma is highly treatable and rarely fatal. Self-skin checks can identify changes in moles that could be an indicator of melanoma. Cancer risk perceptions may influence the uptake of important preventive health behaviors such as self-skin checks. The purpose of this study is to examine cancer risk perception factors associated with those who have checked their skin for signs of skin cancer using the 2017 HINTS data. Retrospective cross-sectional analysis of a nationally representative sample of U.S. adults using the Health Information National Trends Survey (HINTS). Logistic regressions were...
Source: Journal of Cancer Education - Category: Cancer & Oncology Source Type: research
ConclusionsWhether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractIn line with the ongoing phase I trial (NCT03784625) dedicated to melanoma targeted radionuclide therapy (TRT), we explore the interplay between immune system and the melanin ligand [131I]ICF01012 alone or combined with immunotherapy (immune checkpoint inhibitors, ICI) in preclinical models. Here we demonstrate that [131I]ICF01012 induces immunogenic cell death, characterized by a significant increase in cell surface-exposed annexin A1 and calreticulin. Additionally, [131I]ICF01012 increases survival in immunocompetent mice, compared to immunocompromised (29 vs. 24  days,p = 0.0374). Flow cytomet...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractEpidemiological evidence suggests that females have an advantage over males in cases of melanoma incidence, progression, and survival. However, the biological mechanisms underlying these sex differences remain unclear. With the knowledge that females generally have a more robust immune system than males, we investigated sex differences in melanoma progression in a B16-F10/BL6 syngeneic mouse model. We observed significantly less tumor volume and growth rate over 14  days in female mice compared to male mice. Furthermore, higher populations of CD4+ and CD8+ T cells, which indicate adaptive immune responses, wer...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
This study aimed at determining in vitro the antimelanoma activity of OA and the relative mechanism of action. OA induced cell growth inhibition in 501Mel melanoma cells with an IC50 in the low micromolar range of concentrations. Moreover, an OA concentration approximating the IC50 induced G1/S phase arrest, DNA fragmentation, and downregulation of genes encoding antiapoptotic (BCL2 and MCL1) and proproliferative (c-KIT, K-RAS, PIK3R3, mTOR) proteins, while increased transcription levels of the proapoptotic protein BAX. Concordantly, OA increased the levels of miR-193a-3p (targeting MCL1, c-KIT and K-RAS), miR-193a-5p (tar...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
The authors regret that the affiliation details are incorrect for Authors Simone Mocellin and Carlo R. Rossi. The correct affiliation details are given below.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Corrigendum Source Type: research
AbstractPhotosensitizers (PS) are compounds that can generate reactive oxygen species under irradiation of appropriate light and are widely used in photodynamic therapy (PDT). Currently, topical PDT is an effective treatment for several skin diseases, including bacterial infections, fungal mycoses and psoriasis. In addition, PDT is also used to treat non ‐melanoma skin cancer and can be a potential tool for melanoma, associated with other treatments. In this work, we evaluated the antitumor photoactivity of a new pyrene‐based PS (TPPy) by using the murine melanoma cell line (B16F10). Thein vitro permeation/retention te...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: RESEARCH ARTICLE Source Type: research
Conditions:   Clinical Stage IV Cutaneous Melanoma AJCC v8;   Metastatic Malignant Neoplasm in the Central Nervous System;   Metastatic Melanoma;   Pathologic Stage IV Cutaneous Melanoma AJCC v8 Interventions:   Drug: Dabrafenib Mesylate;   Drug: Tazemetostat Hydrobromide;   Drug: Trametinib Dimethyl Sulfoxide Sponsor:   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Lymphedema: Clinical Summary of the ONS Guidelines™ for Cancer Treatment-Related Lymphedema. Clin J Oncol Nurs. 2020 Oct 01;24(5):566-570 Authors: Backler C, Beck M, Poage E Abstract Secondary (acquired) lymphedema is a chronic condition lacking a known cure that most commonly results from cancer treatment, particularly for breast, gynecologic, prostate, and head and neck cancers; lymphoma; and melanoma, and affects an estimated 1 in 1,000 Americans. Lymphedema is characterized by an accumulation of protein-rich lymphatic fluid in the affected part of the body. It can potentially affect function...
Source: Clinical Prostate Cancer - Category: Cancer & Oncology Authors: Tags: Clin J Oncol Nurs Source Type: research
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