Matsuki Eri, Bohn Olga L, El Jamal Siraj, Pichardo Janine D, Zelenetz Andrew D, Younes Anas, Teruya-Feldstein Julie
Lymphoma Service, Department of Medicine.
Department of Pathology, Memorial Sloan Kettering Cancer Center.
Appl Immunohistochem Mol Morphol. 2019 Sep;27(8):572-580. doi: 10.1097/PAI.0000000000000645.
There are multiple prognostic indicators for diffuse large B-cell lymphoma (DLBCL) including the international prognostic index (IPI), and gene expression profiling (GEP) to classify the disease into germinal center B-cell and activated B-cell subtypes, the latter harboring inferior prognosis. More recently, tumor-associated macrophages (TAM) and lymphocyte-to-monocyte ratio (LMR) were found to have prognostic implications in DLBCL. However, consensus is yet to be reached in terms of the significance of each. In this study, we evaluated the prognostic value of TAM as assessed by CD163 or CD68 positivity by immunohistochemistry on tissue biopsies and LMR was calculated from peripheral blood differential, with focus on the inclusion of rituximab as a treatment modality. The number of CD68-positive cells in the tumor microenvironment did not exhibit significant prognostic value, whereas higher number of CD163-positive cells was associated with inferior overall survival in patients treated with chemotherapy alone. This effect was no longer evident in patients treated with rituximab containing chemoimmunotherapy. In contrast, the prognostic significance of LMR on survival was more persistent regardless of treatment. There was no association between LMR and the number of CD163-positive cells. Our results suggest that LMR is the more easily and widely available prognostic marker in this era of chemoimmunotherapy. Our finding supports previous literature that the effect of TAM can vary according to treatment. Interaction between rituximab and TAM warrant further scientific investigation for mechanistic insights into targeted therapeutics.
弥漫性大B细胞淋巴瘤(DLBCL)有多种预后指标,包括国际预后指数(IPI)以及基因表达谱分析(GEP),后者可将该疾病分为生发中心B细胞亚型和活化B细胞亚型,后者预后较差。最近,发现肿瘤相关巨噬细胞(TAM)和淋巴细胞与单核细胞比值(LMR)在DLBCL中具有预后意义。然而,对于它们各自的意义尚未达成共识。在本研究中,我们通过免疫组织化学检测组织活检中CD163或CD68阳性来评估TAM的预后价值,并从外周血分类中计算LMR,重点关注利妥昔单抗作为一种治疗方式的纳入情况。肿瘤微环境中CD68阳性细胞的数量未显示出显著的预后价值,而在单纯接受化疗的患者中,CD163阳性细胞数量较多与较差的总生存期相关。在接受含利妥昔单抗的化疗免疫治疗的患者中,这种效应不再明显。相比之下,无论治疗如何,LMR对生存的预后意义更持久。LMR与CD163阳性细胞数量之间没有关联。我们的结果表明,在这个化疗免疫治疗时代,LMR是更容易获得且应用更广泛的预后标志物。我们的发现支持了先前的文献,即TAM的效应可能因治疗而异。利妥昔单抗与TAM之间的相互作用值得进一步科学研究,以深入了解靶向治疗的机制。