Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas

Int J Mol Sci. 2021 May 23;22(11):5489. doi: 10.3390/ijms22115489.

Abstract

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Keywords: CD8; FoxP3; IDO1; Merkel cell carcinoma; PD-L1.

MeSH terms

  • Adaptive Immunity
  • Age Factors
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Merkel Cell / chemistry
  • Carcinoma, Merkel Cell / immunology
  • Carcinoma, Merkel Cell / mortality*
  • Carcinoma, Merkel Cell / virology
  • Female
  • Forkhead Transcription Factors / analysis
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / virology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Merkel cell polyomavirus / isolation & purification
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Staging
  • Neoplasms, Second Primary / chemistry
  • Neoplasms, Second Primary / immunology
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / virology
  • Prognosis
  • Progression-Free Survival
  • Proportional Hazards Models
  • Sex Factors
  • Skin Neoplasms / chemistry
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / virology
  • Skin Ulcer / etiology
  • T-Lymphocyte Subsets / immunology*
  • Tumor Virus Infections

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Neoplasm Proteins