Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Clinical and Diagnostic Hematology, University Hospital Basel, Basel, Switzerland.
Med. 2021 Feb 12;2(2):180-195.e5. doi: 10.1016/j.medj.2020.10.006. Epub 2020 Dec 3.
Current prognostic variables can only partly explain the large outcome heterogeneity in diffuse large B cell lymphoma (DLBCL). We aimed to investigate the utility of systems-level protein and immune repertoire profiling for outcome prognostication in DLBCL.
In this retrospective study, we used proximity extension assay technology to quantify 81 immune-related proteins in serum or plasma in 2 independent cohorts in a total 111 DLBCL patients. Protein levels were assessed before and after treatment with rituximab and chemotherapy, and the patients were compared with 19 age- and sex-matched healthy blood donors. In a subset of the patients, we performed a broad mass cytometric characterization of immune cell repertoires in peripheral blood.
Patients displayed large deviations in protein profiles compared with healthy controls. Development of a systemic protein deviation (SPD) score provided a 4-protein-based metric that reflected the overall degree of protein deviations compared with age- and sex-matched healthy blood donors. The SPD score identified patients with very poor overall survival in both cohorts and correlated with increased frequencies of peripheral blood PD-1 CD8 T cells, and expansion of myeloid-derived suppressor cells.
Our results show that a simple metric based on measurement of a small set of serum or plasma proteins can be used to probe systemic immune changes associated with poor survival in DLBCL. This finding warrants further investigation in larger, prospective studies to establish a clinical prognostic biomarker.
目前的预后变量只能部分解释弥漫性大 B 细胞淋巴瘤（DLBCL）的大的结果异质性。我们旨在研究系统水平的蛋白质和免疫受体谱分析在 DLBCL 中的预后预测中的应用。
在这项回顾性研究中，我们使用邻近延伸测定技术来定量 2 个独立队列中的 111 例 DLBCL 患者的 81 种与免疫相关的血清或血浆蛋白。在接受利妥昔单抗和化疗治疗前后评估蛋白水平，并与 19 名年龄和性别匹配的健康献血者进行比较。在部分患者中，我们对外周血免疫细胞受体库进行了广泛的质谱细胞特征分析。
与健康对照组相比，患者的蛋白谱显示出较大的偏差。系统性蛋白偏差（SPD）评分的发展提供了一种基于 4 种蛋白的指标，反映了与年龄和性别匹配的健康献血者相比的整体蛋白偏差程度。该 SPD 评分在两个队列中都识别出总体生存率非常差的患者，并且与外周血 PD-1 CD8 T 细胞频率增加以及髓样来源的抑制细胞扩张相关。
我们的结果表明，基于少量血清或血浆蛋白测量的简单指标可用于探测与 DLBCL 不良生存相关的全身性免疫变化。这一发现需要在更大的前瞻性研究中进一步研究，以建立临床预后生物标志物。
