Abstract
Because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 (sPD-1) could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines. Very low levels of sPD-1 may indicate lack of an existing anti-cancer immune response; very high levels may indicate an active immune response that is suppressed. In between these extremes, a decrease in PD-1 following injections of an anti-cancer vaccine may indicate an enhanced immune response that has not been suppressed. Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients treated with a tumor cell vaccine (TCV) and 17 treated with a dendritic cell vaccine (DCV). Survival was better in DCV-treated patients. sPD-1 was measured at week-0, one week before the first of three weekly subcutaneous injections, and at week-4, one week after the third injection. The combination of a very low baseline sPD-1, or absence of a very high PD-1 at baseline followed by a decline in sPD-1 at week-4, was predictive of surviving three or more years in DCV-treated patients, but not TCV-treated. Among DCV-treated patients, these sPD-1 criteria appropriately classified 8/10 (80%) of 3-year survivors, and 6/7 (86%) of patients who did not survive three years. These preliminary observations suggest that sPD-1 might be a useful biomarker for melanoma patients being considered for treatment with this DCV vaccine, and/or to predict efficacy after only three injections, but this would have to be confirmed in larger studies.
Highlights
programmed cell death protein-1 (PD-1) (CD279) was first described by Tasuku Honjo and colleagues at Kyoto University in 1992 [1]
Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients treated with a tumor cell vaccine (TCV) and 17 treated with a dendritic cell vaccine (DCV)
Because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines because it is upregulated on activated lymphocytes by interferon gamma, during a Th1 immune response [6, 8,9,10]
Summary
PD-1 (CD279) was first described by Tasuku Honjo and colleagues at Kyoto University in 1992 [1]. The purpose of this study was to determine the possible use of sPD-1 as an immune marker in patients with metastatic melanoma who were enrolled in a randomized phase II trial testing autologous dendritic cell vaccines (DCV) and autologous tumor cell vaccines (TCV) [11, 12]. We were looking for a surrogate marker that might reflect immune response and association with survival in patients treated with these vaccines. For both products, the antigen source was irradiated autologous cancer cells from short-term cell cultures derived from surgically excised autologous tumor. We asked the following questions: (1) was baseline sPD-1 prognostic for survival in these patients with metastatic melanoma, or for either of the two treatment-defined cohorts; (2) within each treatmentdefined cohort, was either vaccine efficacious in patients with very low sPD-1 levels and/or very high sPD-1 levels; (3) if there was a change in sPD-1 from week0, one week before the first of three weekly vaccine injections, to week-4, one week after the third injection, was this predictive of survival for all patients or in either treatment-defined cohort; and (4) could sPD-1 be used to define cohorts that were prognostic or predictive of survival
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