High prevalence of Merkel cell polyomavirus is associated with dysregulation in transcript levels of TLR9 and type I IFNs in a large cohort of CF patients from the Italian (Lazio) reference center for cystic fibrosis

Bitossi, Camilla; Viscido, Agnese; Prezioso, Carla; Brazzini, Gabriele; Trancassini, Maria; Borrazzo, Cristian; Passerini, Sara; Frasca, Federica; Scordio, Mirko; Sorrentino, Leonardo; Oliveto, Giuseppe; Fracella, Matteo; D’Auria, Alessandra; Selvaggi, Carla; Cimino, Giuseppe; Midulla, Fabio; Pierangeli, Alessandra; Antonelli, Guido; Moens, Ugo; Pietropaolo, Valeria; Scagnolari, Carolina

doi:10.1016/j.micpath.2022.105644

Cited by 2 publications

(1 citation statement)

References 62 publications

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“…MCPyV T antigens inhibit CCAAT/enhancer binding protein (C/EBP) transcription factor, which leads to downregulation of TLR9 ( 43 ). Indeed, a clinical study of cystic fibrosis patients demonstrated lower levels of TLR9 in patients harboring MCPyV ( 44 ). Thus, downregulation of TLR9 in MCC tumors could prevent recruitment of immune cells and may contribute to tumor survival.…”

Section: Requires Multiple Immune Escape Mechanisms At Playmentioning

confidence: 99%

Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas

2023

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Understanding and augmenting cancer-specific immunity is impeded by the fact that most tumors are driven by patient-specific mutations that encode unique antigenic epitopes. The shared antigens in virus-driven tumors can help overcome this limitation. Merkel cell carcinoma (MCC) is a particularly interesting tumor immunity model because (1) 80% of cases are driven by Merkel cell polyomavirus (MCPyV) oncoproteins that must be continually expressed for tumor survival; (2) MCPyV oncoproteins are only ~400 amino acids in length and are essentially invariant between tumors; (3) MCPyV-specific T cell responses are robust and strongly linked to patient outcomes; (4) anti-MCPyV antibodies reliably increase with MCC recurrence, forming the basis of a standard clinical surveillance test; and (5) MCC has one of the highest response rates to PD-1 pathway blockade among all solid cancers. Leveraging these well-defined viral oncoproteins, a set of tools that includes over 20 peptide-MHC class I tetramers has been developed to facilitate the study of anti-tumor immunity across MCC patients. Additionally, the highly immunogenic nature of MCPyV oncoproteins forces MCC tumors to develop robust immune evasion mechanisms to survive. Indeed, several immune evasion mechanisms are active in MCC, including transcriptional downregulation of MHC expression by tumor cells and upregulation of inhibitory molecules including PD-L1 and immunosuppressive cytokines. About half of patients with advanced MCC do not persistently benefit from PD-1 pathway blockade. Herein, we (1) summarize the lessons learned from studying the anti-tumor T cell response to virus-positive MCC; (2) review immune evasion mechanisms in MCC; (3) review mechanisms of resistance to immune-based therapies in MCC and other cancers; and (4) discuss how recently developed tools can be used to address open questions in cancer immunotherapy. We believe detailed investigation of this model cancer will provide insight into tumor immunity that will likely also be applicable to more common cancers without shared tumor antigens.

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Section: Requires Multiple Immune Escape Mechanisms At Playmentioning

confidence: 99%

Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas

2023

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High rates of anal Merkel Cell Polyomavirus and HPV co‐infection among people living with HIV

Passerini,

Fracella,

Benvenuto

et al. 2024

Journal of Medical Virology

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Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high‐risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001).

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High prevalence of Merkel cell polyomavirus is associated with dysregulation in transcript levels of TLR9 and type I IFNs in a large cohort of CF patients from the Italian (Lazio) reference center for cystic fibrosis

Cited by 2 publications

References 62 publications

Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas

Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas

High rates of anal Merkel Cell Polyomavirus and HPV co‐infection among people living with HIV

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