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-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. 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.

中文翻译：

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纳武单抗免疫疗法对口腔鳞状细胞癌患者的免疫学作用。

背景技术尽管检查站封锁已被广泛使用，但对癌症患者，特别是患有口腔鳞状细胞癌（OCSCC）的患者的免疫学影响尚未得到很好的研究。方法本研究评估了抗PD-1（nivolumab）治疗对10例OCSCC患者的免疫学影响。这涉及在nivolumab治疗之前和之后对外周血T细胞亚群及其免疫介质表达的表型分析。重点是治疗的免疫学效应，而不考虑可能的临床反应。结果Nivolumab导致血液CD4 +细胞频率下降，但不影响其IFN-γ的表达。但是，nivolumab增加了表达Treg支持因子Foxp3的CD4 +细胞的比例。Nivolumab治疗导致CD8 +细胞比例增加。虽然它们的颗粒酶B的表达增加，但没有达到意义。CD8 +细胞亚群的分析表明，nivolumab引起非常规CD8dimCD3 + T细胞水平的增加。这些非常规的T细胞以及常规的CD8hiCD3 +细胞也会引起颗粒酶B的表达增加。CD8hiCD3 +亚群的IFN-γ表达也增加了近乎显着。用nivolumab治疗对含CD8dimCD3细胞亚群的NK水平或IFN-γ或颗粒酶B的表达没有影响。结论这些结果表明nivolumab对CD4 +和CD8 +细胞群产生相反的影响，但CD4 +细胞水平却下降，但增加Treg细胞的比例，