Cancer Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Flow Cytometry Core, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Clin Exp Immunol. 2019 Jun;196(3):345-352. doi: 10.1111/cei.13264. Epub 2019 Feb 17.
Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4 CD25 regulatory T cells (conventional T ) with T cells expressing T cell immunoglobulin-3 (TIM-3 ) and latency-associated peptide (LAP) T cells. We found that LAP-expressing T cells were more suppressive than conventional T , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of T and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome T resistance to ICI.
肿瘤免疫逃逸涉及到大量增殖的免疫抑制细胞的扩增和效应 T 细胞增殖的抑制。免疫检查点（IC）阻断了肿瘤反应性 T 细胞的激活途径。肿瘤细胞经常利用这些途径来逃避免疫破坏，通过 IC 抑制剂（ICI）阻断这些途径在多种恶性肿瘤中显示出了有希望的结果。在这项研究中，我们研究了 ICI 药物 pembrolizumab 在体外对各种 T 细胞亚群的影响。我们比较了表达 T 细胞免疫球蛋白-3（TIM-3）和潜伏期相关肽（LAP）的 T 细胞与 CD4 CD25 调节性 T 细胞（常规 T 细胞）的抑制活性。我们发现 LAP 表达的 T 细胞比常规 T 细胞更具有抑制作用，但 TIM-3 表达的 T 细胞没有抑制作用。我们的结果表明，pembrolizumab 不会调节 T 细胞的功能，而是通过释放效应 T 细胞来介导其免疫刺激作用。这些发现可能有助于开发设计干预 IC 途径的药物，以克服 T 细胞对 ICI 的耐药性。
