The Role of Monocytes in non-Hodgkin Lymphoma

肿瘤微环境在非霍奇金淋巴瘤中的作用及其意义 肿瘤内免疫细胞在淋巴瘤病理中的作用一直被严重低估。瘤内 单核细胞和巨噬细胞尤为重要，我们的数据表明，肿瘤内 非霍奇金淋巴瘤中的单核细胞具有高度的免疫抑制作用，支持恶性细胞的生长。 在前期工作中，我们发现外周血中有大量的抑制性单核细胞。 改善淋巴瘤患者的血液和肿瘤微环境，促进淋巴瘤细胞的存活。SMCS 保护淋巴瘤细胞免受化疗诱导的细胞死亡，促进淋巴瘤细胞植入 严重联合免疫缺陷(SCID)小鼠。此外，我们还发现，淋巴结内的SMC 表达包括B7-H1(PD-L1，CD273)在内的免疫抑制配体，抑制正常T细胞增殖和 促进FoxP3+调节性T细胞的诱导。这些初步研究表明，SMC有一个 对恶性NHL细胞和非恶性瘤内T细胞的影响。 根据我们的结果，我们假设免疫系统和恶性肿瘤之间的交集 非霍奇金淋巴瘤的细胞是SMC。在这项提议中，我们计划了解单核细胞是否特别 被招募到淋巴瘤部位，哪些特异性趋化因子可以被抑制以防止SMC迁移； 淋巴瘤细胞如何诱导SMC支持其恶性细胞生长并抑制宿主的抗肿瘤作用 免疫；以及是否促进单核/巨噬细胞成熟或抑制它们与 其他细胞，特别是在有单抗存在的情况下，可以改善它们的抗肿瘤功能。vt.在.的基础上 这个项目的完成，我们希望对单核细胞的作用和他们的 非霍奇金淋巴瘤的后代。总而言之，我们的发现可能会产生重大影响，导致有效的 淋巴瘤患者的单核细胞导向治疗方法。

The tumor microenvironment plays an important role in non-Hodgkin lymphoma (NHL) and the role intratumoral immune cells play in the pathology of lymphoma has been significantly understated. Intratumoral monocytes and macrophages are particularly important and our data demonstrate that intratumoral monocytes in NHL are highly immunosuppressive and support malignant cell growth. In preliminary work, we found that suppressive monocytic cells (SMCs) are abundant within the peripheral blood and tumor microenvironment in lymphoma patients and promote the survival of lymphoma cells. SMCs protect lymphoma cells from chemotherapy-induced cell death and promote lymphoma cell engraftment into severe combined immunodeficient (SCID) mice. Furthermore, we found that SMCs within lymph nodes express immunosuppressive ligands including B7-H1 (PD-L1, CD273), inhibit normal T-cell proliferation and promote the induction of FoxP3+ regulatory T cells. These preliminary studies suggest that SMCs have an effect on both malignant NHL cells and non-malignant intratumoral T-cells. Based on our results, we hypothesize that the intersection between the immune system and the malignant cell in NHL is the SMCs. In this proposal, we plan to understand whether monocytes are specifically recruited to sites of lymphoma and which specific chemokines could be inhibited to prevent SMC migration; how lymphoma cells induce SMCs to support their malignant cell growth and to suppress the host's antitumor immunity; and whether promoting monocyte/macrophage maturation or inhibiting their interaction with other cells, particularly in the presence of monoclonal antibodies, improves their anti-tumor function. Upon completion of this project, we expect to have a greater understanding of the role of monocytes and their progeny in NHL. Collectively our findings are likely to have a major impact by leading to an effective monocyte-directed therapeutic approach for patients with lymphoma.