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首页> 外文期刊>Nature >PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
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PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity

机译：肿瘤相关巨噬细胞的PD-1表达抑制吞噬作用和肿瘤免疫力

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摘要

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance(1,2). Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system(3,4). Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma(5-9). Although it is well established that PD-1-PD-L1 blockade activates T cells, little is known about the role that this pathway may have in tumour-associated macrophages (TAMs). Here we show that both mouse and human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models of cancer and with increasing disease stage in primary human cancers. TAM PD-1 expression correlates negatively with phagocytic potency against tumour cells, and blockade of PD-1-PD-L1 in vivo increases macrophage phagocytosis, reduces tumour growth and lengthens the survival of mice in mouse models of cancer in a macrophage-dependent fashion. This suggests that PD-1-PD-L1 therapies may also function through a direct effect on macrophages, with substantial implications for the treatment of cancer with these agents.
机译：程序性细胞死亡蛋白1（PD-1）是一种免疫检查点受体，可在活化T细胞上调以诱导免疫耐受（1,2）。肿瘤细胞经常过表达PD-1的配体，即程序性细胞死亡配体1（PD-L1），促进其从免疫系​​统逃逸（3,4）。通过与配体或受体结合而阻断PD-1和PD-L1之间相互作用的单克隆抗体在患有多种癌症（包括黑素瘤，结肠直肠癌，非小细胞肺癌）的患者中显示出显着的临床疗效和霍奇金淋巴瘤（5-9）。尽管已经公认PD-1-PD-L1阻滞激活了T细胞，但对于这种途径在肿瘤相关巨噬细胞（TAM）中的作用知之甚少。在这里，我们显示小鼠和人类TAM都表达PD-1。在原发性人类癌症的癌症小鼠模型中，TAM PD-1的表达随时间增加，并且随着疾病阶段的增加而增加。 TAM PD-1的表达与针对肿瘤细胞的吞噬能力呈负相关，并且体内阻断PD-1-PD-L1会增加巨噬细胞的吞噬作用，降低肿瘤的生长，并以巨噬细胞依赖的方式延长小鼠在癌症模型中的存活。这表明PD-1-PD-L1疗法也可能通过对巨噬细胞的直接作用而起作用，这对于用这些药剂治疗癌症具有实质性的意义。

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  • 来源
    《Nature》 |2017年第7655期|495-499|共5页
  • 作者

    Gordon Sydney R.; Aute Roy L. M.; Dulken Ben W.; Hutter Gregor; George Benson M. .; Ccracken Melissa N. M.; Gupta Rohit; Tsai Jonathan M. .; Sinha Rahul; Corey Daniel; Ring Aaron M. .; Connolly Andrew J.; Weissman Irving L.;

  • 作者单位

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Stanford Med Scientist Training Program, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA|Univ Hosp Basel, Dept Neurosurg, CH-4031 Basel, Switzerland;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Human Immune Monitoring Ctr Biobank, Palo Alto, CA 94304 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06519 USA;

    Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA|Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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