Heterogeneity of programmed death‐ligand expression in a case of Merkel cell carcinoma exhibiting complete regression after multiple metastases

Nakamura, Minoru; Magara, Tetsuya; Kobayashi, Yuka; Kato, Hiroyuki; Watanabe, Shun; Morita, Akimichi

doi:10.1111/bjd.17430

Cited by 8 publications

(8 citation statements)

References 6 publications

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“…Patient characteristics and treatments are summarized in Table 1 . This cohort mostly overlaps with the cohort in our previous reports ( 10 , 11 ), and the 41 cases for which RNA sequencing was performed are the same.…”

Section: Methodsmentioning

confidence: 76%

“…Including immature TLSs, in which only a few CD3-positive cells surround a CD20-positive cell cluster, if a lesion had at least one TLS, it was counted as TLS-positive, as previously described ( 12 ). The fluorescence intensities of PD-L1 were calculated from 10 randomly selected fields using ImageJ Software (NIH, Bethesda, MD, USA) as previously described ( 11 ). After evaluating entire specimens, CD8-positive cells and PD-1-positive cells were counted in several locations having a high density of infiltrating cells, and the mean value was calculated.…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction and sequencing were performed for 41 randomly selected samples as previously described ( 11 ). Tumor tissue was carefully dissected from 3 to 5 undyed formalin-fixed paraffin-embedded tissue sections (4-µm thick) using a scalpel blade and deparaffinized in 640 µl deparaffinization solution (Qiagen, Hilden, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Tertiary Lymphoid Structures and Chemokine Landscape in Virus-Positive and Virus-Negative Merkel Cell Carcinoma

et al. 2022

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Tertiary lymphoid structures (TLSs) are used as biomarkers in many cancers for predicting the prognosis and assessing the response to immunotherapy. In Merkel cell carcinoma (MCC), TLSs have only been examined in MCPyV-positive cases. Here, we examined the prognostic value of the presence or absence of TLSs in 61 patients with MCC, including MCPyV-positive and MCPyV-negative cases. TLS-positive samples had a significantly better prognosis than TLS-negative samples. MCPyV-positive samples had a good prognosis with or without TLSs, and MCPyV-negative/TLS-positive samples had a similarly good prognosis as MCPyV-positive samples. Only MCPyV-negative/TLS-negative samples had a significantly poor prognosis. All cases with spontaneous regression were MCPyV-positive/TLS-positive. We also performed a comprehensive analysis of the chemokines associated with TLS formation using next-generation sequencing (NGS). The RNA sequencing results revealed 5 chemokine genes, CCL5, CCR2, CCR7, CXCL9, and CXCL13, with significantly high expression in TLS-positive samples compared with TLS-negative samples in both MCPyV-positive and MCPyV-negative samples. Only 2 chemokine genes, CXCL10 and CX3CR1, had significantly different expression levels in the presence or absence of MCPyV infection in TLS-negative samples. Patients with high CXCL13 or CCL5 expression have a significantly better prognosis than those with low expression. In conclusion, the presence of TLSs can be a potential prognostic marker even in cohorts that include MCPyV-negative cases. Chemokine profiles may help us understand the tumor microenvironment in patients with MCPyV-positive or MCPyV-negative MCC and may be a useful prognostic marker in their own right.

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Section: Methodsmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

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Tertiary Lymphoid Structures and Chemokine Landscape in Virus-Positive and Virus-Negative Merkel Cell Carcinoma

et al. 2022

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“…Although PD‐L1 expression in MCC provides clues as to whether the tumor is immunologically “hot” or “cold”, its clinical use as a prognostic or efficacy marker is difficult due to its high heterogeneity within individual patients. 48 We reported that PD‐L1 levels are uniform if multiple primary lesions that appeared at the same time are resected at the same time and immunostained under the same conditions. In that case, surgical invasion results in increased PD‐L1 expression.…”

Section: Immunological Biomarkers Of MCCmentioning

confidence: 96%

“…Tumor PD‐L1 expression is used to predict the ICI response in other cancer types, but it is not used as a companion diagnostic in MCC. Although PD‐L1 expression in MCC provides clues as to whether the tumor is immunologically “hot” or “cold”, its clinical use as a prognostic or efficacy marker is difficult due to its high heterogeneity within individual patients 48 . We reported that PD‐L1 levels are uniform if multiple primary lesions that appeared at the same time are resected at the same time and immunostained under the same conditions.…”

Section: Immunological Biomarkers Of MCCmentioning

confidence: 98%

Immune activity in Merkel cell carcinoma

Nakamura

Morita

2021

The Journal of Dermatology

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Merkel cell carcinoma (MCC) is widely known as a highly malignant skin cancer. The pathogenesis of MCC, however, remains mysterious due to the extremely small number of cases and its prevalence in the elderly. Despite its high‐grade malignancy, spontaneous regression occurs with some frequency. The immune activity of the tumor underlies this peculiar behavior. In recent years, immune checkpoint blockade therapies, including the anti‐programmed death ligand 1 antibody, have provided successful results. These therapies, however, are ineffective in approximately half the patients with advanced MCC and few treatments are available for those patients. In this review, we summarize the increasing body of evidence relating to the immune activity of MCC and immunological biomarkers. The interesting and sometimes peculiar behavior of MCC, such as their spontaneous regression, is largely due to their high immunosensitivity. Understanding the tumor immunokinetics of MCC should provide critical insight for understanding cancer immunotherapy. Here, we introduce a new classification for MCC according to its immune activity. Combined application of programmed death ligand 1 (a prognostic factor and predictor of the efficacy of immune checkpoint inhibitors in various cancers) with glucose‐6‐phosphate dehydrogenase (a new promising biomarker for MCC) may enable classification of MCC based on its immune status. Whether the new classification can be used to predict the efficacy of immune checkpoint blockade therapies remains to be evaluated in future studies, but the classification may facilitate future treatment selection.

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Increased programmed death ligand-1 expression in metastatic Merkel cell carcinoma associates with better prognosis

Nakamura

Magara

Nojiri

et al. 2020

Journal of Dermatological Science

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Heterogeneity of programmed death‐ligand expression in a case of Merkel cell carcinoma exhibiting complete regression after multiple metastases

Cited by 8 publications

References 6 publications

Tertiary Lymphoid Structures and Chemokine Landscape in Virus-Positive and Virus-Negative Merkel Cell Carcinoma

Tertiary Lymphoid Structures and Chemokine Landscape in Virus-Positive and Virus-Negative Merkel Cell Carcinoma

Immune activity in Merkel cell carcinoma

Increased programmed death ligand-1 expression in metastatic Merkel cell carcinoma associates with better prognosis

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