Identifying dysfunctional T-cell signatures in patients with aggressive diffuse large B cell lymphoma (DLBCL).

“重新唤醒”和重新引导免疫系统的治疗方法在晚期恶性肿瘤患者中显示出巨大的前景。“唤醒”免疫系统可以使用双特异性抗体(BsAbs)来实现。这些细胞在一只手臂上与肿瘤细胞结合，在另一只手臂上与正常T细胞结合，从而产生一种免疫突触，从而促进肿瘤的破坏。BsAbGlofitamab与B细胞特异性CD20和T细胞特异性CD3结合。在早期临床试验中，接受Glofitamab治疗的淋巴瘤患者中有50%进入持久的完全缓解状态；Glofitamab是迄今为止最有效的CD20抗体。然而，并不是所有的患者都有反应，原因也不清楚。一种可能是淋巴瘤患者的T细胞功能受损。令人惊讶的是，免疫系统的功能在DLBCL患者中还没有广泛的特征。因此，本研究的目的是使用多参数流式细胞术、单细胞蛋白质组学和RNA测序的方法来确定DLBCL中T细胞群体的性质和功能。端粒长度将与TeloNostiX合作确定。这些数据将与来自原发肿瘤的整个外显子组测序数据相结合，并将确定在治疗的早期阶段使用BsAbs的最佳条件。

Therapies that "reawaken" and redirect the immune system have shown huge promise in patients with advanced malignancy. "Reawakening" the immune system can be achieved using bispecific antibodies (BsAbs). These bind to tumour cells on one arm and to normal T cells on the other, thereby creating an immune synapse which facilitates tumour destruction. The BsAb glofitamab binds to the B cell specific CD20 and T-cell-specific CD3. 50% of lymphoma patients receiving glofitamab in early phase clinical trials entered a durable complete remission; glofitamab is the most potent CD20 antibody to date. Nevertheless, not all patients respond and the reasons for this are not clear. One possibility is that the T-cell functions are impaired in lymphoma patients. Surprisingly, functions of the immune system have not been extensively characterised in patients with DLBCL.The aims of this study are therefore to determine the nature and functions of T cell populations in DLBCL using a multiomic approach (multi-parameter flow cytometry, single cell proteomics and RNA Sequencing). Telomere length will be determined in collaboration with TeloNostiX. These data will be integrated with whole exome sequencing data from primary tumours and will define optimal conditions for the use of BsAbs in earlier phases of treatment.