Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Blog Article
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 Puzzle 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 Socks often respond to anti-PD-1 therapy.