Intratumoral delivery of plasmid interleukin-12 via electroporation leads to regression of injected and non-injected tumors in Merkel cell carcinoma.
CONCLUSIONS: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL-12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer. PMID: 31582519 [PubMed - as supplied by publisher]
Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer for which immune modulation by immune checkpoint inhibitors show remarkable response rates. However, primary or secondary resistance to immunotherapy prevents benefits in a significant proportion of patients. For MCC, one immune escape mechanism is insufficient recognition by T cells due to downregulation of major histocompatibility complex (MHC) class I surface expression. Histone deacetylase (HDAC) inhibitors have been demonstrated to epigenetically reverse low MHC class I expression caused by downregulation of the antigen processing machinery (APM).
Conclusions: SSA could be a valid therapeutic option in patients with MCC with high SR expression. When combined with PD-1/PD-L1 immune-checkpoint inhibition, SSA is likely to enhance antiproliferative activity. Our case report provides the rationale to conduct a prospective trial and translational research to verify the efficacy and safety of combined SSA and checkpoint inhibitors for advanced MCC.
In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues. PMID: 32623581 [PubMed - as supplied by publisher]
Merkel cell carcinoma (MCC) is a rare and highly metastatic neuroendocrine skin cancer. The majority of MCC tumors are virus positive (VP-MCC) and are associated with integrated Merkel cell polyomavirus, whereas the remainder of MCC are virus-negative (VN-MCC) tumors that are characterized by ultraviolet light associated mutations. Metastatic MCC is treated by immunotherapy or chemotherapy. Conventional chemotherapy is usually unbeneficial in MCC, and although immune checkpoint inhibitor (ICI) therapy can be effective, it is contraindicated in many patients and others have disease progression despite immunotherapy.
Merkel cell carcinoma (MCC) is an aggressive skin cancer that often recurs. MCC tumors can respond to PD-1 pathway inhibitors rapidly, however, it is unclear how often these responses persist after discontinuation of therapy. We retrospectively assessed 159 persons with advanced MCC treated with first-line anti-PD-(L)1 agents. Non-responders were defined as those with progressive disease (PD) or stable disease (SD), while responders had partial response (PR), or complete response (CR), based on clinician assessment.
arma Terry A. Day Cancers that arise in the head and neck region are comprised of a heterogeneous group of malignancies that include carcinogen- and human papillomavirus (HPV)-driven mucosal squamous cell carcinoma as well as skin cancers such as cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. These malignancies develop in critical areas for eating, talking, and breathing and are associated with substantial morbidity and mortality despite advances in treatment. Understanding of advances in the management of these various cancers is important for all multidisciplinary prov...
AbstractSkin cancers remain the most common group of cancers globally, and the incidence continues to rise. Although localized skin cancers tend to have excellent outcomes following surgical excisions, the less common cases that become surgically unresectable or metastatic have been associated with poor prognosis and suboptimal treatment responses to cytotoxic chemotherapy. Development of monoclonal antibodies to programmed cell death-1 receptor and its ligand (PD-1/PD-L1) have transformed the management of metastatic melanoma, squamous cell carcinoma, and Merkel cell carcinoma. These agents, as monotherapies, are associat...
Purpose of review Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, which is associated in 80% of cases with the Merkel cell polyomavirus (MCPyV). Advanced stages respond to immune checkpoint inhibitors in 50% of cases. Major issues remain unanswered regarding its oncogenesis and optimal treatment. Recent findings MCPyV-negative and MCPyV-positive MCCs have been hypothesized to derive from distinct cells, although the cell of origin remains a matter of debate. The crucial role the MCPyV small T oncoprotein was recently confirmed by its ability to inactivate p53, together with its contribution to the me...
Over the past several years, a wave of new cancer immunotherapy agents referred to as immune checkpoint inhibitors (ICIs) have transformed the standard of care for patients with cancer. ICIs are most commonly used in advanced cancers with palliative intent and recently as frontline therapy for some cancers. These new agents have been shown to extend overall survival (OS) and progression free survival (PFS) in patients with lung cancer, melanoma, Hodgkin lymphoma, renal cell carcinoma, urothelial carcinoma, Merkel cell carcinoma, head and neck cancer, and more.
CONCLUSIONS: Our explorative study identified new tumor tissue-based molecular characteristics associated with response to anti-PD-1/PD-L1 therapy in MCC. These observations warrant further investigations in larger patient cohorts to confirm their potential value as predictive markers. PMID: 31932494 [PubMed - as supplied by publisher]