scholarly journals Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5301
Author(s):  
Robert A. Szczepaniak Sloane ◽  
Michael G. White ◽  
Russell G. Witt ◽  
Anik Banerjee ◽  
Michael A. Davies ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Cytotoxic T Lymphocyte ◽  
Mechanisms Of Resistance ◽  
Term Survival ◽  
Programmed Cell Death 1 ◽  
Melanoma Treatment ◽  
Melanoma Patients ◽  
Poor Outcomes ◽  
Insight Into

Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors.

scholarly journals Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab

2015 ◽  
Vol 51 (17) ◽  
pp. 2689-2697 ◽  
Author(s):  
Zeynep Eroglu ◽  
Dae Won Kim ◽  
Xiaoyan Wang ◽  
Luis H. Camacho ◽  
Bartosz Chmielowski ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Term Survival ◽  
Long Term Survival

The demise of #NSFW: Contested platform governance and Tumblr’s 2018 adult content ban

2021 ◽  
pp. 146144482199671
Author(s):  
Jeanna Sybert
Keyword(s):  
Core Values ◽  
Term Survival ◽  
Long Term Survival ◽  
Community Values ◽  
Critical Moment ◽  
Platform Governance ◽  
Sexually Explicit ◽  
Explicit Content ◽  
Insight Into

On December 3, 2018, Tumblr announced that it would ban sexually explicit content from the platform, drawing immediate backlash from users. The ensuing discord on the site is conceptualized here as contested platform governance, or a conflict between users and ownership, in which not only are a platform’s policies and features challenged, but also its core values, identity, and/or purposes are put into question. By examining 238 Tumblr posts, this analysis identifies the unique ways users combatted the ban and (re)inscribed community values, while also contesting the owners’ legitimacy to govern the platform. Holding implications for the site’s long-term survival, such conflicts capture a critical moment in which the boundaries of power between users and ownership are challenged and, possibly, transformed. By examining Tumblr’s Not Safe For Work (NSFW) ban through the lens of platform governance, this study offers insight into how power and its limits are negotiated online.

scholarly journals Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha

2018 ◽  
Vol 38 (11) ◽  
pp. 6393-6397 ◽  
Author(s):  
KALLE MATTILA ◽  
PIRITA RAANTA ◽  
VALTTERI LAHTELA ◽  
SEPPO PYRHÖNEN ◽  
ILKKA KOSKIVUO ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Combination Chemotherapy ◽  
Stage Iv ◽  
Term Survival ◽  
Long Term Survival ◽  
Melanoma Patients ◽  
Stage Iv Melanoma ◽  
Intermediate Dose

scholarly journals Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy

2020 ◽  
Vol 21 (19) ◽  
pp. 7139 ◽  
Author(s):  
Elena Shklovskaya ◽  
Helen Rizos
Keyword(s):  
Tumor Microenvironment ◽  
Patient Outcomes ◽  
Cytotoxic T Lymphocyte ◽  
Cell Types ◽  
Development Of Resistance ◽  
Improve Patient Selection ◽  
Potential Biomarker ◽  
Programmed Cell Death 1 ◽  
Tumor Biopsies

Immunotherapies blocking immune inhibitory receptors programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on T-cells have dramatically improved patient outcomes in a range of advanced cancers. However, the lack of response, and the development of resistance remain major obstacles to long-term improvements in patient outcomes. There is significant interest in the clinical use of biomarkers to improve patient selection, and the expression of PD-1 ligand 1 (PD-L1) is often reported as a potential biomarker of response. However, accumulating evidence suggests that the predictive value of PD-L1 expression in tumor biopsies is relatively low due, in part, to its complex biology. In this review, we discuss the biological consequences of PD-L1 expression by various cell types within the tumor microenvironment, and the complex mechanisms that regulate PD-L1 expression at the genomic, transcriptomic and proteomic levels.

scholarly journals Evolving impact of long-term survival results on metastatic melanoma treatment

2020 ◽  
Vol 8 (2) ◽  
pp. e000948 ◽  
Author(s):  
Olivier Michielin ◽  
Michael B Atkins ◽  
Henry B Koon ◽  
Reinhard Dummer ◽  
Paolo Antonio Ascierto
Keyword(s):  
Targeted Therapies ◽  
Survival Data ◽  
Long Term Results ◽  
Tumor Type ◽  
Term Survival ◽  
Long Term Survival ◽  
The Past ◽  
Number Of Patients ◽  
Melanoma Treatment

Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

scholarly journals Clinicopathologic features associated with efficacy and long-term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors

Cancer ◽  
2015 ◽  
Vol 121 (21) ◽  
pp. 3826-3835 ◽  
Author(s):  
Alexander M. Menzies ◽  
James S. Wilmott ◽  
Martin Drummond ◽  
Serigne Lo ◽  
Megan Lyle ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Clinicopathologic Features ◽  
Term Survival ◽  
Mek Inhibitors ◽  
Long Term Survival ◽  
Melanoma Patients

scholarly journals Pembrolizumab dramatically resolves choroidal metastatis from esophageal adenocarcinoma and restores vision: a case report

2021 ◽  
Vol 2021 (6) ◽  
Author(s):  
Dianne Barrett ◽  
Andrew Sumnicht ◽  
KV Chalam ◽  
Micheal Rauser
Keyword(s):  
Case Report ◽  
Esophageal Adenocarcinoma ◽  
Term Survival ◽  
Gastrointestinal Malignancy ◽  
Poor Vision ◽  
Aggressive Cancer ◽  
Programmed Cell Death 1 ◽  
Ocular Metastasis

ABSTRACT Esophageal adenocarcinoma historically is an aggressive cancer with poor long-term survival. Ocular metastasis secondary to gastrointestinal malignancy is rare. In managing patients with ocular metastasis, quality of life (specifically vision preservation) is one of the most important factors patients and providers consider when deciding on a treatment regimen. Anti-programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors such as pembrolizumab have shown promising results as second-line therapy for patient with metastatic malignancy. We describe a novel case of a functionally monocular patient with known metastatic esophageal adenocarcinoma who developed poor vision and a large choroidal lesion in his better seeing eye. The lesion regressed and vision restored to 20/20 after treatments with pembrolizumab in this case report.

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