Abstract
BackgroundAlthough checkpoint blockades have become widely used, the immunological impact in cancer patients, especially those with oral cavity squamous cell carcinoma (OCSCC), has not been well studied.MethodsThe present study assessed the immunological impact of anti-PD-1 (nivolumab) treatment in 10 patients with OCSCC. This involved phenotypic analyses of peripheral blood T-cell subpopulations and their expression of immune mediators prior to and following nivolumab treatment. The focus was on immunological effects of treatment without regard to possible clinical responses.ResultsNivolumab caused a decline in the frequency of blood CD4+ cells but did not affect their expression of IFN-γ. However, nivolumab increased the proportion of CD4+ cells expressing the Treg-supporting factor Foxp3. Nivolumab treatment caused an increase in the proportion of CD8+ cells. While their expression of granzyme B increased, it did not attain significance. Analyses of CD8+ cell subpopulations showed nivolumab caused an increase in levels of unconventional CD8dimCD3+ T-cells. It also caused an increase in expression of granzyme B by these unconventional T-cells as well as by the conventional CD8hiCD3+ cells. The CD8hiCD3+ subpopulation also had a near-significant increase in IFN-γ expression. Treatment with nivolumab had no effect on the levels of the NK containing CD8dimCD3− subpopulation of cells or their expression of IFN-γ or granzyme B.ConclusionsThese results show nivolumab causes opposing effects on CD4+ and CD8+ cell populations, with CD4+ cell levels declining but increasing the proportion of Treg cells, and unconventional CD8+ T-cell levels increasing with increased expression of immune mediators by CD8+ T-cell subpopulations.
Highlights
Checkpoint blockades have become widely used, the immunological impact in cancer patients, especially those with oral cavity squamous cell carcinoma (OCSCC), has not been well studied
Thyroid dysfunction associated with treatment of advanced melanoma patients with the anti-programmed cell death-1 (PD-1) antibody pembrolizumab was associated with increases in circulating CD56+CD16+ natural killer (NK) cells and increased HLA-DR expression on CD14+CD16+ monocytes compared to levels in healthy controls [8]
Since the objective of this study was to assess the immunologic impact of anti-PD-1 therapy, the phenotypic analyses of peripheral blood leukocytes were analyzed independent of preliminary clinical evaluation
Summary
Checkpoint blockades have become widely used, the immunological impact in cancer patients, especially those with oral cavity squamous cell carcinoma (OCSCC), has not been well studied. Checkpoint inhibitors such as those targeting programmed cell death-1 (PD-1) are becoming widely used in cancer treatment regimens. There is substantial indirect evidence of immune activation resulting from anti-PD-1 antibody treatment Such evidence includes the immune-associated adverse events in patients receiving treatment. Thyroid dysfunction associated with treatment of advanced melanoma patients with the anti-PD-1 antibody pembrolizumab was associated with increases in circulating CD56+CD16+ natural killer (NK) cells and increased HLA-DR expression on CD14+CD16+ monocytes compared to levels in healthy controls [8]
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