Abstract

The pathogenesis of 80% of Merkel cell carcinoma (MCC) cases is associated with Merkel cell polyomavirus (MCPyV). Forkhead helix transcription factor P3 (FOXP3) and the T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)–CD155 pathway, which are targets for immunotherapy, were assessed as prognostic factors of MCC. We analyzed mRNA expression data of 111 patients with MCC and performed immunohistochemical analysis to detect the expression of programmed death ligand 1 (PD-L1), CD8, FOXP3, TIGIT, and CD155 in 65 cases of MCC. In CD8 and FOXP3 immunostaining, the number of expressing-infiltrating cells was determined by dividing the region into tumor center and invasive front areas. FOXP3 expression was evaluated separately in cells with high and low intensities. Aberrant TIGIT expression and weak CD155 staining were observed in MCC cells. CD8- and FOXP3-positive cell infiltrations were higher in the invasive front than in the tumor center. Multivariate Cox hazard analysis revealed that high infiltration of cells with low-intensity FOXP3 expression in the invasive front is a favorable prognostic factor (p = 0.025). Thus, targeting TIGIT–CD155 signaling and FOXP3 as well as PD-L1 may be a therapeutic strategy for MCC.

Details

Title
Clinical significance of the expression of FOXP3 and TIGIT in Merkel cell carcinoma
Author
Iwasaki, Takeshi 1 ; Hayashi, Kazuhiko 2 ; Matsushita, Michiko 3 ; Nonaka, Daisuke 4 ; Matsumoto, Takamasa 1 ; Taniguchi, Midori 1 ; Kuwamoto, Satoshi 2 ; Umekita, Yoshihisa 2 ; Oda, Yoshinao 1 

 Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
 Tottori University, Department of Pathology, School of Medicine, Faculty of Medicine, Yonago, Japan (GRID:grid.265107.7) (ISNI:0000 0001 0663 5064) 
 Tottori University, Department of Pathology, School of Medicine, Faculty of Medicine, Yonago, Japan (GRID:grid.265107.7) (ISNI:0000 0001 0663 5064); Tottori University, Department of Pathobiological Science and Technology, School of Health Science, Faculty of Medicine, Yonago, Japan (GRID:grid.265107.7) (ISNI:0000 0001 0663 5064) 
 The Guy’s and St. Thomas’ NHS Foundation Trust, Department of Cellular Pathology, London, UK (GRID:grid.420545.2) 
Pages
13114
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2849397150
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.