TY  - JOUR
AU  - Toberer, Ferdinand
AU  - Winkler, Julia K
AU  - Atienza Fernandez, Leroy
AU  - Adams, Lea
AU  - Brobeil, Alexander
AU  - Tóth, Marcell
AU  - Enk, Alexander H
AU  - Becker, Jürgen
AU  - Lonsdorf, Anke
TI  - Inhibitory Immune Checkpoints beyond Programmed Cell Death Ligand 1 in Merkel Cell Carcinoma: Abundant Expression of TIGIT Independent of the Presence of Merkel Cell Polyoma Virus.
JO  - Acta dermato-venereologica
VL  - 105
SN  - 0001-5555
CY  - Uppsala
PB  - Acta Dermato-Venereologica
M1  - DKFZ-2025-01339
SP  - adv42882
PY  - 2025
N1  - DKFZ-ZMBH Alliance
AB  - Merkel cell carcinoma is a rare, aggressive skin cancer in which Merkel cell polyoma virus (MCPyV) is frequently pathogenically involved. After failure of anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy, therapeutic options for advanced disease are limited. The contribution of the coinhibitory checkpoint molecule T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), a regulator of exhausted CD8+ T cells, to the immunosuppressive Merkel cell carcinoma microenvironment is understudied. This study evaluated the immunohistochemical expression of tumour (Tumor Proportion Score, TPS) and infiltrating immune cells (Immune Cell Score, ICS) for programmed cell death ligand 1, TIGIT, its high-affinity receptor CD155, and CD8 in 21 primary Merkel cell carcinoma and 6 metastases. Unlike CD155, TIGIT was abundantly expressed by tumour and immune cells and independent of the MCPyV status, determined by RT-PCR. Programmed cell death ligand 1+ immune cells were significantly increased in TIGIT TPS-positive and MCPyV-positive primary MCC along with significant intercorrelations of programmed cell death ligand 1 and TIGIT immune cell expression and CD8+ infiltrates. Programmed cell death ligand 1 IC-positivity correlated with superior disease-specific survival. The data indicate that TIGIT may contribute to local immune dysfunction in Merkel cell carcinoma, beyond programmed cell death ligand 1 and independent of MCPyV, and provide a rationale to further explore TIGIT as a potential target for Merkel cell carcinoma immunotherapy.
KW  - Humans
KW  - Carcinoma, Merkel Cell: immunology
KW  - Carcinoma, Merkel Cell: virology
KW  - Carcinoma, Merkel Cell: secondary
KW  - Carcinoma, Merkel Cell: mortality
KW  - Carcinoma, Merkel Cell: pathology
KW  - Receptors, Immunologic: analysis
KW  - Receptors, Immunologic: genetics
KW  - Receptors, Immunologic: metabolism
KW  - Skin Neoplasms: immunology
KW  - Skin Neoplasms: virology
KW  - Skin Neoplasms: pathology
KW  - Skin Neoplasms: mortality
KW  - Male
KW  - Merkel cell polyomavirus: immunology
KW  - Merkel cell polyomavirus: isolation & purification
KW  - Female
KW  - Aged
KW  - B7-H1 Antigen: analysis
KW  - B7-H1 Antigen: metabolism
KW  - Polyomavirus Infections: immunology
KW  - Polyomavirus Infections: virology
KW  - Middle Aged
KW  - Aged, 80 and over
KW  - Tumor Microenvironment
KW  - Tumor Virus Infections: immunology
KW  - Tumor Virus Infections: virology
KW  - Lymphocytes, Tumor-Infiltrating: immunology
KW  - Biomarkers, Tumor: analysis
KW  - Biomarkers, Tumor: genetics
KW  - CD8-Positive T-Lymphocytes: immunology
KW  - Receptors, Virus: analysis
KW  - TIGIT protein, human (NLM Chemicals)
KW  - Receptors, Immunologic (NLM Chemicals)
KW  - B7-H1 Antigen (NLM Chemicals)
KW  - CD274 protein, human (NLM Chemicals)
KW  - poliovirus receptor (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Receptors, Virus (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40590417
C2  - pmc:PMC12235568
DO  - DOI:10.2340/actadv.v105.42882
UR  - https://inrepo02.dkfz.de/record/302799
ER  -