Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications

Abstract: We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/great...
Source: The American Journal of Dermatopathology - Category: Pathology Tags: Original Study Source Type: research

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CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Publication date: Available online 28 October 2019Source: Journal of Geriatric OncologyAuthor(s): Andrea Sbrana, Rachele Antognoli, Giuseppe Pasqualetti, Giuseppe Linsalata, Chukwma Okoye, Valeria Calsolaro, Federico Paolieri, Francesco Bloise, Sergio Ricci, Andrea Antonuzzo, Fabio MonzaniAbstractBackgroundOlder adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy.Patients and Meth...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Authors: KamiƄska-Winciorek G, Cybulska-Stopa B, Lugowska I, Ziobro M, Rutkowski P Abstract The introduction of immunotherapy into the treatment of cancer patients has revolutionised the oncological approach and significantly improved patient survival. The key drugs are immune checkpoint inhibitors (CPIs), whose mechanism of action is to elicit immune response against cancer cell antigens. Three types of CPIs are currently used and approved: an anti-CTLA-4 antibody, ipilimumab; anti-PD-1 antibodies, nivolumab and pembrolizumab; and anti-PD-L1 antibodies: atezolizumab, avelumab and durvalumab. CPIs have been widely...
Source: Advances in Dermatology and Allergology - Category: Dermatology Tags: Postepy Dermatol Alergol Source Type: research
This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group.Implications for Practice.Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyomav...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Melanoma and Cutaneous Malignancies Source Type: research
Conclusion: In our knowledge, there is a little number of cases of MCC reported in literature. Surgical management is considered in cases with intracranial hypertension or focal signs. The adjuvant treatment options are immunotherapy and radiotherapy. PMID: 31583169 [PubMed]
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
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]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date. The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018. The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node bi...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Abstract Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers. ...
Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer that is highly immunogenic. Approximately 80% of MCC tumors are virus positive (VP-MCC) and express Merkel cell polyomavirus (MCPyV) T antigens that drive oncogenesis. As VP-MCC have a low mutation burden with few predicted neoantigens, viral oncogenes are thought to be the primary target for anti-cancer immunity. Immune checkpoint inhibitors improve MCC survival, yet
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research
Snoeck Merkel cell carcinoma (MCC) is an aggressive type of skin cancer whose main causative agent is Merkel cell polyomavirus (MCPyV). MCPyV is integrated into the genome of the tumor cells in most MCCs. Virus-positive tumor cells constitutively express two viral oncoproteins that promote cell growth: the small (sT) and the large (LT) tumor antigens (TAs). Despite the success of immunotherapies in patients with MCC, not all individuals respond to these treatments. Therefore, new therapeutic options continue to be investigated. Herein, we used CRISPR/Cas9 to target the viral oncogenes in two virus-positive MCC cell li...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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