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Updated: Mar 21, 2026
Author Spotlight: Unlocking Insights into the Immune Cell Landscape of Tumors
Published on: August 18, 2023
Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma
Laurence Feldmeyer1,2, Courtney W Hudgens2, Genevieve Ray-Lyons3
1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose:
Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. Because programmed death ligand-1 (PD-L1) is frequently expressed in MCC, immune checkpoint blockade has been leveraged as treatment for metastatic disease. There is therefore a critical need to understand the relationships between MCPyV status, immune profiles, and patient outcomes.
Experimental Design:
IHC for CD3, CD8, PD-1, PD-L1, and MCPyV T-antigen (to determine MCPyV status) was performed on 62 primary MCCs with annotated clinical outcomes. Automated image analysis quantified immune cell density (positive cells/mm2) at discrete geographic locations (tumor periphery, center, and hotspot). T-cell receptor sequencing (TCRseq) was performed in a subset of MCCs.
Results:
No histopathologic variable associated with overall survival (OS) or disease-specific survival (DSS), whereas higher CD3+ (P = 0.004) and CD8+ (P = 0.037) T-cell density at the tumor periphery associated with improved OS. Higher CD8+ T-cell density at the tumor periphery associated with improved DSS (P = 0.049). Stratifying MCCs according to MCPyV status, higher CD3+ (P = 0.026) and CD8+ (P = 0.015) T-cell density at the tumor periphery associated with improved OS for MCPyV+ but not MCPyV- MCC. TCRseq revealed clonal overlap among MCPyV+ samples, suggesting an antigen-specific response against a unifying antigen.
Conclusions:
These findings establish the tumor-associated immune infiltrate at the tumor periphery as a robust prognostic indicator in MCC and provide a mechanistic rationale to further examine whether the immune infiltrate at the tumor periphery is relevant as a biomarker for response in ongoing and future checkpoint inhibitor trials in MCC. Clin Cancer Res; 22(22); 5553-63. ©2016 AACR.
Insights
Immune cell density at the tumor periphery is a strong predictor of survival in Merkel cell carcinoma (MCC). Higher T-cell infiltration in Merkel cell carcinoma patients indicates a better prognosis, especially in virus-positive cases.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor outcomes.
- Programmed death ligand-1 (PD-L1) expression in MCC suggests potential for immune checkpoint blockade therapy.
- Understanding the interplay between Merkel cell polyomavirus (MCPyV) status, immune profiles, and patient survival is crucial.
Purpose of the Study:
- To investigate the prognostic significance of immune cell infiltration in Merkel cell carcinoma.
- To explore the relationship between MCPyV status, tumor microenvironment, and patient survival.
- To identify potential biomarkers for response to immune checkpoint inhibitors in MCC.
Main Methods:
- Immunohistochemistry (IHC) for CD3, CD8, PD-1, PD-L1, and MCPyV T-antigen on 62 primary MCC samples.
- Automated image analysis to quantify immune cell density at tumor periphery, center, and hotspot.
- T-cell receptor sequencing (TCRseq) performed on a subset of samples.
Main Results:
- No histopathologic variables correlated with overall survival (OS) or disease-specific survival (DSS).
- Increased CD3+ and CD8+ T-cell density at the tumor periphery associated with improved OS and DSS.
- In MCPyV-positive MCC, higher peripheral CD3+ and CD8+ T-cell density correlated with improved OS.
- TCRseq indicated clonal overlap in MCPyV-positive MCC, suggesting an antigen-specific immune response.
Conclusions:
- Tumor-associated immune infiltrate at the periphery serves as a prognostic indicator in MCC.
- Peripheral immune infiltrate may be a relevant biomarker for checkpoint inhibitor response in MCC trials.
- Findings support further investigation of peripheral immune markers for guiding MCC treatment strategies.
