Immunological effects of nivolumab immunotherapy in patients with oral cavity squamous cell carcinoma

Background: Although 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. Methods: The 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. Results: Nivolumab caused a decline in the frequency of blood CD4(+) cells but did not affect their expression of IFN-gamma. 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 CD8(dim)CD3(+) T-cells. It also caused an increase in expression of granzyme B by these unconventional T-cells as well as by the conventional CD8(hi)CD3(+) cells. The CD8(hi)CD3(+) subpopulation also had a near-significant increase in IFN-gamma expression. Treatment with nivolumab had no effect on the levels of the NK containing CD8(dim)CD3(-) subpopulation of cells or their expression of IFN-gamma or granzyme B. Conclusions: These 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.