Predominance of central memory T cells with high T-cell receptor repertoire diversity is associated with response to PD-1/PD-L1 inhibition in Merkel cell carcinoma.

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]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

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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).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
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.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Clin Transl Oncol Source Type: research
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.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pharmacology and Drug Development Source Type: research
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.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Translational Studies Source Type: research
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...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research
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...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: MELANOMA AND OTHER SKIN NEOPLASMS: Edited by Céleste Lebbe Source Type: research
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.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Source Type: research
Publication date: Available online 3 January 2020Source: Seminars in Cancer BiologyAuthor(s): Kelly Olino, Tristen Park, Ntia AhujaAbstractAdvances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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