title: Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas.
abstract: Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra- and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Behr
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Wiebke K
authors.initials: WK
authors.lastname: Peitsch
authors.affiliation: Department of Neurology, University Hospital Heidelberg Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hametner
authors.affiliation: Institute of Pathology, University Hospital Heidelberg Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Dermatology, Julius Maximilians University Würzburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Houben
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schönhaar
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Michel
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dollt
authors.affiliation: Department of Dermatology, Julius Maximilians University Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Goebeler
authors.affiliation: Department of Pathology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Schmieder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D059965:Merkel cell polyomavirus / Q000302:isolation & purification; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human
keywords: Merkel cell carcinoma; PD-L1; immune cell infiltration; tertiary lymphoid structures