Marconato Maddalena, Maringer Yacine, Walz Juliane S, Nelde Annika, Heitmann Jonas S
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.
Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
Cancers (Basel). 2022 Sep 25;14(19):4659. doi: 10.3390/cancers14194659.
Chronic lymphocytic leukemia (CLL) is characterized by recurrent relapses and resistance to treatment, even with novel therapeutic approaches. Despite being considered as a disease with low mutational burden and thus poor immunogenic, CLL seems to retain the ability of eliciting specific T cell activation. Accordingly, we recently found non-mutated tumor-associated antigens to play a central role in CLL immunosurveillance. Here, we investigated the association of total and CLL-exclusive HLA class I and HLA class II peptide presentation in the mass spectrometry-defined immunopeptidome of leukemic cells with clinical features and disease outcome of 57 CLL patients. Patients whose CLL cells present a more diverse immunopeptidome experienced fewer relapses. During the follow-up phase of up to 10 years, patients with an HLA class I-restricted presentation of high numbers of total and CLL-exclusive peptides on their malignant cells showed a more favorable disease course with a prolonged progression-free survival (PFS). Overall, our results suggest the existence of an efficient T cell-based immunosurveillance mediated by CLL-associated tumor antigens, supporting ongoing efforts in developing T cell-based immunotherapeutic strategies for CLL.
慢性淋巴细胞白血病（CLL）的特点是反复复发且对治疗产生耐药性，即使采用新型治疗方法也是如此。尽管CLL被认为是一种突变负担低因而免疫原性差的疾病，但它似乎仍保留引发特异性T细胞活化的能力。因此，我们最近发现非突变的肿瘤相关抗原在CLL免疫监视中起核心作用。在此，我们研究了白血病细胞质谱定义的免疫肽组中总HLA I类和HLA II类以及CLL特异性HLA I类和HLA II类肽呈递与57例CLL患者的临床特征和疾病转归之间的关联。CLL细胞呈现更多样化免疫肽组的患者复发次数较少。在长达10年的随访期内，恶性细胞上HLA I类限制性呈递大量总肽和CLL特异性肽的患者疾病进程更有利，无进展生存期（PFS）延长。总体而言，我们的结果表明存在由CLL相关肿瘤抗原介导的基于T细胞的有效免疫监视，支持目前为CLL开发基于T细胞的免疫治疗策略的努力。
