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Patients may be influenced by immune function at the tumor site, which may lead to improved patient outcomes. We review patient samples of metastatic melanoma, a tumor responder to T cell-based therapies, and find that tumor-infiltrating T cells are mainly compared to CD14+ monocytes/macrophages rather than melanoma cells. Stromal CD14+ cells within tumor nests have a distinctive transcriptional signature that distinguishes them from CD14+ cells. The stromal CD14+ cell signature also indicates a candidate biomarker, and it suggests that reprogramming stromal macrophages to DC function may provide a therapeutic option for metastatic cancers.
Source link: https://doi.org/10.1016/j.xcrm.2022.100621
In melanoma specimens, there are variations in GILT protein expression in malignant melanocytes. However, the correlation of GILT in metastatic melanoma in patients treated with ICI and the cell type expressing GILT linked to survival has yet to be established. In patients treated with ICI, the use of RNA sequencing results, as well as increased metastatic melanoma mRNA expression in metastatic melanoma specimens was correlated with improved progression-free and overall survival. In 100% and 65% of metastatic melanoma samples, respectively, Positive GILT immunohistochemical staining in antigen presenting cells and melanoma cells was found. In the clinical study's subset of patients treated with ICI, high GILT protein expression in melanoma cells was associated with improved overall survival. These results show that increased GILT mRNA expression in bulk tumor samples and elevated GILT protein expression in melanoma cells is associated with improved survival in ICI-treated patients.
Source link: https://doi.org/10.3390/cancers14092200
The ability of residual tumor cells to persist in a dormant state, without proliferation, is one of the key factors that contributed to decreased response to therapy. This comprehensive review, aimed at determining the underlying causes of dormancy/awakening disease in metastatic melanoma, will help determine the most effective therapy options that will kill melanoma circulating tumor cells or hold them in the dormant state for life, thus reducing tumor formation and metastatic dissemination.
Source link: https://doi.org/10.3390/cancers14092104
Patients with BRAFV600-mutant metastatic melanoma have been treated with immune-checkpoint inhibitors and BRAF/MEK-directed targeted therapy, which has enhanced the treatment landscape for patients with BRAFV600-mutant metastatic melanoma. Although TT allows for rapid disease detection, secondary TT resistance increases the duration of responses, although TT allows for rapid disease detection. We found 135 patients with BRAF-mutated, metastatic melanoma who underwent consecutive treatment with TT followed by CPI, or vice versa, as first and second-line therapy respectively in this retrospective, single-center, real-world review. Patients receiving front-line CPI also had significantly higher objective response rates to second-line medications, which was even higher. Our results showed that rapid disease progression was less common in patients treated with front-line CPI, and that subsequent treatment with TT resulted in improved survival rates. In a subgroup of previously untreated BRAF-mutant metastatic melanoma patients, sequential administration of front-line CPI is associated with improved tumor control and overall survival.
Source link: https://doi.org/10.3390/cancers14092082
In the kinome of metastatic melanoma cells relative to primary tumors, the present research determines changes in gene expression and isoform ratios. Between 103 primary tumor and 367 metastatic samples from The Cancer Genome Atlas, we examine 538 total kinases and 3,040 identified kinase isoforms between 103 primary tumor and 367 metastatic samples. We find five examples of splicing events that are favored in metastatic studies using exon junction mapping. In metastatic melanoma, we show inconsistent apoptosis and protein localization among SLK isoforms. Notably, separate samples with BRAF hotspot mutations and RAS hotspot mutations are distinguished by distinct DE and DIR patterns, the latter of which lacks effective kinase inhibitor therapies. RAS mutants' DE in RAS mutants focuses on CMGC kinases rather than RTKs as in BRAF mutants. Our findings reveal a new angle in therapeutic target identification and demonstrate how specific mutational subtypes may respond differently to drugs highlighting potential new driver events in cancer.
Source link: https://doi.org/10.1371/journal.pcbi.1010065
Patients with metastatic melanoma can have long-term effects, and immunoe checkpoint inhibitors can cause long-term reactions. We recently compared matched primary and metastatic melanoma lesions of patients with ipilimumab's compared tumor mutational burden, HLA-ABC status, and tumor infiltrating lymphocytes of patients with ipilimumab to determine the effect of ICI treatment success. To assess the effect of tumor mutational burden, TME and ICI treatment success, we directly compared matched primary and metastatic melanoma.
Source link: https://doi.org/10.1136/jitc-2021-004329
To determine the transition from primary melanoma to metastasis, we looked at single-cell transcriptome profiles of parental B16 melanoma cells and its highly metastatic subclone. In B16F10 cells, the number of cycling cells and cells with a high ratio of Kdm5b was highly expressed. The C4 cluster comprised both B16F0 and B16F10 cells and demonstrated intermediate DEG patterns, whereas the B16 cluster mostly consisted of B16F10 cells and displayed typical metastatic characteristics, with typical metastatic characteristics. Our findings reveal deeper insight into melanoma metastasis at the single-cell level, assisting in future research into melanoma metastasis control.
Source link: https://doi.org/10.1016/j.bbrc.2022.05.003
Here, we used advanced functional genomics to interrogate 9,000 human tumors and multiple single-cell sequencing sets using benchmarked T cell lines, extensive T cell differentiation trajectories, human and mouse vaccine responses, and other human TILs. T memory/resident memory services were found throughout solid tumors, relative to other T cell states. A large number of memory/resident memory-scoring TILs in anti-PD-1 responders, according to Trajectory results, which extended post therapy.
Source link: https://doi.org/10.1016/j.ccell.2022.04.005
Nivolumab and ipilimumab are two immune checkpoint inhibitors that can effectively stimulate the native T cell response and result in an antitumor response. ICIs are, on the other hand, are at a higher risk of cutaneous immune-related adverse events. In patients with metastatic melanoma, we report a fatal case of SJS associated with nivolumab and a non-fatal case of TEN with nivolumab/ipilimumab combination therapy. Since weeks or months on checkpoint inhibitor therapy, it is not unusual to see SJS or TEN.
Source link: https://doi.org/10.36849/JDD.6559
Small bowel blockage in a man in his early 50s has been found, necessitating emergency laparoscopic small bowel biopsy for the metastatic melanoma of the jejunum with no apparent primary lesion. Diaphragation, constipation, and exhaustion occurred a week after his first experience with ipilimumab and nivolumab, he was left with diffuse abdominal pain, constipation, and exhaustion. a generalized motor seizure occurred on day 15, and despite plasmapheresis later that day, the patient died from fatal immune-related thrombocytopenic purpura.
Source link: https://doi.org/10.3389/fimmu.2022.871217
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