<scp>PD</scp>‐1 and <scp>PD‐L1</scp> in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma

Mitteldorf, Christina; Berisha, Arbeneshe; Tronnier, Michael; Pfaltz, Monique C.; Kempf, Werner

doi:10.1111/cup.12973

Cited by 33 publications

(27 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results confirm previously published data [ 10 – 15 ] and extend these observations to the identification of specific T-cell, macrophage and B-cell subsets whose presence is associated with MCPyV. Our data concerning PDL1 expression are largely consistent with those recently published by Walsh and coworkers [ 11 ], i.e., PDL1 is mainly expressed by peritumoral macrophages rather than neoplastic cells [ 13 , 23 ]: in our series, PDL1 expression by neoplastic cells was observed in just 22/179 (12%) cases, a slightly lower proportion than that found by Wehkamp et al and Benigni et al [ 24 , 25 ]. Our results are basically consistent with those of Miller et al, who showed that MCPyV-positive tumors had a strikingly more clonal intratumoral TCR repertoire than MCPyV-negative tumors [ 26 ].…”

Section: Discussionsupporting

confidence: 93%

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment

et al. 2020

View full text Add to dashboard Cite

Aims Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1. Methods and results In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells.

show abstract

Section: Discussionsupporting

confidence: 93%

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Immunohistochemical staining of 8 VN-MCC and 34 VP-MCC showed that none of the VN tumors expressed PD-L1, while 50% of the VP-MCCs were positive for PD-L1 [ 199 ]. Another study on 14 MCC (6 VN and 8 VP) reported that 1 VN-MCC had few (1%) PD-L1 positive tumors cells, whereas 7 of the VP-MCC were PD-L1 positive with 2–7.5% of the cells expressing PD-L1 [ 200 ]. It is not known whether MCPyV can affect the expression of PD-L1, but upregulation of PD-L1 has been observed in persistent infection with the oncoviruses hepatitis B and C [ 201 ].…”

Section: Immune Evasion Of Vp-mccmentioning

confidence: 99%

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Pietropaolo¹,

Prezioso

Moens

2020

Cancers

View full text Add to dashboard Cite

Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed.

show abstract

“…Previous work has suggested that proinflammatory cytokine release by T cells is enhanced with PD-1 axis blockade [ 15 ]. Moreover, patients with untreated CLL and MCC are known to have an expanded myeloid derived suppressor cell (MDSC) compartment [ 16 ] and MDSC compartment at the tumor microenvironment interface [ 17 ], respectively. RT may have rapidly depleted MDSCs and allowed for unchecked elaboration of pro-inflammatory cytokines [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokine release syndrome after radiation therapy: case report and review of the literature

Barker

Kim

Budhu

et al. 2018

j. immunotherapy cancer

100

102

View full text Add to dashboard Cite

BackgroundCytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic.Case presentationA 65 year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases. Within hours of each weekly dose of RT, he experienced fever, tachycardia, hypotension, rash, dyspnea, and rigors. Based on clinical suspicion for CRS, blood cytokine measurements were performed 1 h after the second and third dose of RT and demonstrated tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels approximately ten-fold higher than normal. These were near normal immediately prior to the third dose of RT, and resolved to normal levels 3 weeks after RT. He experienced rapid regression of irradiated tumors, with development of new sites of metastases soon thereafter. A literature review revealed no clinical cases of CRS after RT for cancer.ConclusionsRT during anti-PD1 immunotherapy in a patient with underlying immune dysfunction appeared to be the putative mediator of an immune process which yielded significant increases in pro-inflammatory cytokines, and produced the clinical symptoms meeting the definition of grade 3 CRS. This case demonstrates the capability of RT to elicit immune-related adverse events.

show abstract

PD‐1 and PD‐L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma

Cited by 33 publications

References 41 publications

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Cytokine release syndrome after radiation therapy: case report and review of the literature

Contact Info

Product

Resources

About