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

Miller, Natalie J.; Church, Candice D.; Fling, Steven P.; Kulikauskas, Rima; Ramchurren, Nirasha; Shinohara, Michi M.; Kluger, Harriet M.; Bhatia, Shailender; Lundgren, Lisa; Cheever, Martin A.; Topalian, Suzanne L.; Nghiem, Paul

doi:10.1186/s40425-018-0450-7

Table 1 Pre-treatment virus-specific B and T cell reactivities in 17 patients with MCPyV-positive MCC receiving pembrolizumab

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

Patient no.	Antibodies to small T-antigen^a	MCPyV tetramer analysis^b	MCPyV intracellular cytokine reactivity^c	Response assessed by RECIST 1.1^d
3	+	+	–	CR
7	+	+	–	CR
8	+	+	+	PR
6	+	+	–	PR
9	+	+	–	PD
16	+	+	–	PR
12	+	–	–	PR
21	+	–	–	CR
19	+	–	+	PD
4	+	N/A	–	PR
13	+	N/A	–	PR
26	+	N/A	–	PR
23	+	N/A	–	PD
15	+	N/A	–	PD
25	+	N/A	–	PR
14	–	N/A	–	CR
10	–	–	+	PR

^a Baseline serum samples from all patients were used to measure MCPyV small T-antigen oncoprotein antibody titers at Laboratory Medicine (University of Washington, Seattle, WA) as described [6]. Titers above 74 STU were considered positive as negative control sera titers fall below 74 STU [7]
^b All patients were low-resolution HLA class I genotyped to determine eligibility for CD8 T cell specific MCPyV peptide-HLA class I tetramer screening (Bloodworks Northwest, Seattle, WA). Pre- and post-treatment peripheral blood mononuclear cells (PBMCs) collected from patients with HLA class I types that corresponded to available MCPyV-specific tetramers (A*02:01, A*24:02, B*07:02, B*35:02, or B*37:01; n = 17 patients) were stained with appropriate tetramers and analyzed by flow cytometry. Samples with > 0.01% of CD8+ T cells co-staining with tetramers were considered positive. N/A (Not Available): nine patients, regardless of tumor viral status, had HLA class I types not amenable to tetramer staining and could thus not be evaluated for the presence of T cells recognizing MCPyV
^c PBMCs pre-treatment and post-treatment blood collections (week 12 or 21) were stimulated with pools of MCPyV-specific peptides in a flow cytometry-based intracellular cytokine secretion assay (HIV Vaccine Trials Network, Seattle, WA). PBMCs that secreted interferon-gamma and/or IL-2 robustly (≥0.1% of CD8 T cells after background subtraction) were considered reactive to MCPyV
^d Abbreviations for RECIST 1.1 response criteria are as follows: CR complete response, PR partial response, PD progressive disease

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Patient no.	Antibodies to small T-antigen^a	MCPyV tetramer analysis^b	MCPyV intracellular cytokine reactivity^c	Response assessed by RECIST 1.1^d
3	+	+	–	CR
7	+	+	–	CR
8	+	+	+	PR
6	+	+	–	PR
9	+	+	–	PD
16	+	+	–	PR
12	+	–	–	PR
21	+	–	–	CR
19	+	–	+	PD
4	+	N/A	–	PR
13	+	N/A	–	PR
26	+	N/A	–	PR
23	+	N/A	–	PD
15	+	N/A	–	PD
25	+	N/A	–	PR
14	–	N/A	–	CR
10	–	–	+	PR

Patient no.	Antibodies to small T-antigen^a	MCPyV tetramer analysis^b	MCPyV intracellular cytokine reactivity^c	Response assessed by RECIST 1.1^d
3	+	+	–	CR
7	+	+	–	CR
8	+	+	+	PR
6	+	+	–	PR
9	+	+	–	PD
16	+	+	–	PR
12	+	–	–	PR
21	+	–	–	CR
19	+	–	+	PD
4	+	N/A	–	PR
13	+	N/A	–	PR
26	+	N/A	–	PR
23	+	N/A	–	PD
15	+	N/A	–	PD
25	+	N/A	–	PR
14	–	N/A	–	CR
10	–	–	+	PR

Patient no.	Antibodies to small T-antigen^a	MCPyV tetramer analysis^b	MCPyV intracellular cytokine reactivity^c	Response assessed by RECIST 1.1^d
3	+	+	–	CR
7	+	+	–	CR
8	+	+	+	PR
6	+	+	–	PR
9	+	+	–	PD
16	+	+	–	PR
12	+	–	–	PR
21	+	–	–	CR
19	+	–	+	PD
4	+	N/A	–	PR
13	+	N/A	–	PR
26	+	N/A	–	PR
23	+	N/A	–	PD
15	+	N/A	–	PD
25	+	N/A	–	PR
14	–	N/A	–	CR
10	–	–	+	PR