经典霍奇金淋巴瘤 (cHL) 中的霍奇金细胞和里德-斯滕伯格 (HRS) 细胞主动改变免疫肿瘤微环境 (TME)，吸引免疫抑制细胞并表达抑制分子。 TME 中骨髓细胞的高频率与不良预后相关，但更具体和稀有的细胞群缺乏精确的标记。骨髓源性抑制细胞 (MDSC) 已在 cHL 患者的外周血中被发现，它们似乎与疾病的侵袭性相关。 TNFRSF9 (CD137) 是一种由单核细胞和树突状细胞表达的 T 细胞共刺激因子。它的表达也在 HRS 细胞中得到描述，被认为在减少抗肿瘤反应中发挥作用。在这里，我们对淋巴细胞和 MDSC 亚型进行定性和定量分析，并使用多重免疫荧光和自动多光谱成像确定 cHL 原发性肿瘤中 CD137 细胞的分布。结果与患者的临床特征相关。细胞用特定的免疫检查点标记物组（PD-1、PD-L1、CD137）、肿瘤浸润 T 淋巴细胞（CD3、PD-1）和单核细胞/MDSC（CD68、CD14、CD33、Arg-1）进行染色。 ，CD11b）。这种方法使我们能够识别不同的表型并分析免疫亚群和肿瘤细胞之间的空间相互作用。结果证实了 T、单核细胞和 HRS 细胞表达 CD137。此外，恶性HRS细胞附近CD137、T耗竭细胞和单核MDSC（m-MDSC）的表达与较差的预后相关。我们的研究结果揭示了 TME 介导免疫逃逸的新元素，并确认 CD137 是 cHL 免疫治疗的候选靶点。© 2024 作者。经泰勒许可出版

The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.