Biology Department, Rider University, Lawrenceville, New Jersey, United States.
Biology Department, Rider University, Lawrenceville, New Jersey, United States.
Immunobiology. 2019 Jan;224(1):94-101. doi: 10.1016/j.imbio.2018.10.004. Epub 2018 Nov 3.
Tumors may include a high proportion of immune modulatory cells and molecules that restrain the anti-cancer response. Activation of T cells to eliminate cancer cells within the immune-suppressive tumor microenvironment remains a challenge. We have shown that C57BL/6 J peritoneal cell culture models features of macrophage-dense tumors as TCR ligation fails to activate T cells unless IFNγ is neutralized or iNOS is inhibited. We tested other forms of T cell activation and found phytohemagglutinin (PHA) distinctive in the ability to markedly expand CD8 T cells in this model. IFNγ or iNOS inhibition was not necessary for this response. PHA triggered less IFNγ production and inhibitory PD-L1 expression than TCR ligation. Macrophages and CD44 T cells bound PHA. Spleen T cell responses to PHA were markedly enhanced by the addition of peritoneal cells revealing that macrophages enhance T cell expansion. That PHA increases CD8 T cell responses within macrophage-dense culture suggests this mitogen might enhance anti-tumor immunity.
肿瘤可能包含大量免疫调节细胞和分子，这些细胞和分子抑制了抗癌反应。在免疫抑制性肿瘤微环境中激活 T 细胞以消除癌细胞仍然是一个挑战。我们已经表明，C57BL/6J 腹膜细胞培养模型具有巨噬细胞密集型肿瘤的特征，因为 TCR 交联不能激活 T 细胞，除非中和 IFNγ 或抑制 iNOS。我们测试了其他形式的 T 细胞激活，发现植物血凝素 (PHA) 在这种模型中具有显著扩增 CD8 T 细胞的能力。这种反应不需要 IFNγ 或 iNOS 抑制。PHA 引发的 IFNγ 产生和抑制性 PD-L1 表达少于 TCR 交联。PHA 与巨噬细胞和 CD44 T 细胞结合。添加腹膜细胞可显著增强脾 T 细胞对 PHA 的反应，表明巨噬细胞增强了 T 细胞的扩增。PHA 增加巨噬细胞密集培养物中 CD8 T 细胞反应表明，这种有丝分裂原可能增强抗肿瘤免疫。
