Fas and FasL interaction induces apoptotic cell death. In immunocompetent cells it plays a crucial role in the effector functions of the cells and in the regulation of host immune response. In tumours (e.g. melanoma), FasL expression possibly counteracts the Fas-positive effector T cells that infiltrate into tumours, and consequently the Fas/FasL interaction can contribute to the escape of tumour cells from the systemic immune response. In this study we examined differences in Fas and FasL expression on cells from the hamster melanotic melanoma line (Ma) and a more aggressive amelanotic melanoma line (Ab). We also tried to find out whether the Fas/FasL expression induces an ability to undergo spontaneous apoptosis in these two transplantable melanoma lines. Our previous studies have shown that cells of the Ma line have a higher ability to undergo spontaneous apoptosis than cells of the Ab line. Isolated transplantable melanoma cells were incubated for 4 and 24 hours and after that time the expression of Fas and FasL was estimated by flow cytometry. The results show that there was no Fas expression, although FasL was detected on both melanoma cell lines. Therefore the data reported by other authors indicate that a lack or a low level of Fas expression and an ectopic expression of FasL on melanoma cells can be an escape mechanism of the tumour, to avoid host immune responses. The content of FasL-positive melanotic melanoma cells was higher than in amelanotic melanoma cells and increased with the prolongation of the incubation time. FasL expression on amelanotic melanoma cells was detected after 24 hours at a level similar to that on melanotic melanoma cells after 4 hours incubation time. FasL expression on melanoma cells can induce apoptosis in cytotoxic T lymphocytes and NK cells which are responsible for tumour cells elimination. The results obtained suggest that the Fas/FasL system does not play any significant role in spontaneous apoptosis of two melanoma cell lines. But these results may indicate the presence of immune privilege of tumour cells with FasL expression.
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http://dx.doi.org/10.2478/v10042-008-0041-4 | DOI Listing |
Drug Des Devel Ther
January 2025
Department of Pharmaceutical Analysis, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People's Republic of China.
Purpose: The incidence of malignant melanoma (MM) has risen over the past three decades, and despite advancements in treatment, there is still a need to improve treatment modalities. This study developed a promising strategy for tumor-targeted co-delivery of Dacarbazine (DTIC) and miRNA 34a-loaded PHRD micelles (Co-PHRD) for combination treatment of MM.
Methods: To construct the dual drug-loaded delivery system Co-PHRD, poly (L-arginine)-poly (L-histidine)-polylactic acid (PLA) was employed as a building block.
Cancer Metab
January 2025
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
Background: In malignant melanoma, liver metastases significantly reduce survival, even despite highly effective new therapies. Given the increase in metabolic liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), this study investigated the impact of liver sinusoidal endothelial cell (LSEC)-specific alterations in MASLD/MASH on hepatic melanoma metastasis.
Methods: Mice were fed a choline-deficient L-amino acid-defined (CDAA) diet for ten weeks to induce MASH-associated liver fibrosis, or a CDAA diet or a high fat diet (HFD) for shorter periods of time to induce early steatosis-associated alterations.
Sci Rep
January 2025
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymphatic vessel involvement in regulating tumor growth and immune response may provide new therapeutic targets or treatment plans to enhance the efficacy of existing therapies. We utilized a syngeneic murine melanoma model in which we surgically disrupted the lymphatic vessel network draining from the tumor to the tumor-draining lymph node (TDLN) while leaving the TDLN intact.
View Article and Find Full Text PDFAm J Clin Dermatol
January 2025
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Individualized neoantigen-directed therapy represents a groundbreaking approach in melanoma treatment that leverages the patient's own immune system to target cancer cells. This innovative strategy involves the identification of unique immunogenic neoantigens (mutated proteins specific to an individual's tumor) and the development of therapeutic vaccines that either consist of peptide sequences or RNA encoding these neoantigens. The goal of these therapies is to induce neoantigen-specific immune responses, enabling the immune system to recognize and destroy cancer cells presenting the targeted neoantigens.
View Article and Find Full Text PDFJ Cell Mol Med
February 2025
Department of Chemotherapy, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Tumour cells possess a multitude of chemoresistance mechanisms, which could plausibly contribute to the ineffectiveness of chemotherapy. O-methylguanine-DNA methyltransferase (MGMT) is an important effector protein associated with Temozolomide (TMZ) resistance in various tumours. To some extent, the expression level of MGMT determines the sensitivity of cells to TMZ, but the mechanism of its expression regulation has not been fully elucidated.
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