Format

Send to

Choose Destination
J Immunother Cancer. 2018 Nov 27;6(1):131. doi: 10.1186/s40425-018-0450-7.

Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy.

Author information

1
Department of Medicine, Divisions of Dermatology and Medical Oncology, University of Washington, 850 Republican Street, Seattle, WA, 98109, USA.
2
Cancer Immunotherapy Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Comprehensive Cancer Center, Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA.
4
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
5
Department of Surgery, Johns Hopkins University School of Medicine, and Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA.
6
Department of Medicine, Divisions of Dermatology and Medical Oncology, University of Washington, 850 Republican Street, Seattle, WA, 98109, USA. pnghiem@uw.edu.

Abstract

BACKGROUND:

Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy.

METHODS:

Immune responses were assessed in patients (n = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment. MCPyV-oncoprotein antibodies were quantified and T cells were assessed for MCPyV-specificity via tetramer staining and/or cytokine secretion. Pre-treatment tumor biopsies were analyzed for T cell receptor clonality.

RESULTS:

MCPyV oncoprotein antibodies were detectable in 15 of 17 (88%) of virus-positive MCC (VP-MCC) patients. Antibodies decreased in 10 of 11 (91%) patients with responding tumors. Virus-specific T cells decreased over time in patients who had a complete response, and increased in patients who had persistent disease. Tumors that were MCPyV(+) had a strikingly more clonal (less diverse) intratumoral TCR repertoire than virus-negative tumors (p = 0.0001).

CONCLUSIONS:

Cancer-specific T and B cell responses generally track with disease burden during PD-1 blockade, in proportion to presence of antigen. Intratumoral TCR clonality was significantly greater in VP-MCC than VN-MCC tumors, suggesting expansion of a limited number of dominant clones in response to fewer immunogenic MCPyV antigens. In contrast, VN-MCC tumors had lower clonality, suggesting a diverse T cell response to numerous neoantigens. These findings reveal differences in tumor-specific immunity for VP-MCC and VN-MCC, both of which often respond to anti-PD-1 therapy.

KEYWORDS:

Anti-PD-1; Immunotherapy; Merkel cell carcinoma; Merkel cell polyomavirus; Pembrolizumab; T cell; Viral cancer antigen

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center