Backert Linus, Kowalewski Daniel Johannes, Walz Simon, Schuster Heiko, Berlin Claudia, Neidert Marian Christoph, Schemionek Mirle, Brümmendorf Tim H, Vucinic Vladan, Niederwieser Dietger, Kanz Lothar, Salih Helmut Rainer, Kohlbacher Oliver, Weisel Katja, Rammensee Hans-Georg, Stevanovic Stefan, Walz Juliane Sarah
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany.
Oncotarget. 2017 Jul 4;8(27):43915-43924. doi: 10.18632/oncotarget.14918.
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape. We found the cancer HLA peptidome datasets to cluster specifically along entity and lineage lines, suggesting that the immunopeptidome directly reflects the differences in the underlying (tumor-)biology. In line with these findings, we only detected a small set of entity-spanning antigens, which were predominantly characterized by low presentation frequencies within the different patient cohorts. These findings suggest that design of T-cell immunotherapies for the treatment of HM should ideally be conducted in an entity-specific fashion.
血液系统恶性肿瘤（HM）是免疫治疗干预的高度适宜靶点，可通过基于抗原特异性T细胞的治疗得到有效治疗。最近的研究表明，某些HM实体中生理上出现的抗癌T细胞反应靶向广泛呈现的非突变表位。因此，HLA配体被认为是广泛适用的抗原特异性现成化合物的主要靶点。为了评估不同HM之间共享的共同靶点的存在情况，这可能使我们能够针对更多患者群体，我们对四个主要HM（19个急性髓系白血病、16个慢性髓系白血病、35个慢性淋巴细胞白血病和13个多发性骨髓瘤/套细胞淋巴瘤样本）的83个基于质谱的HLA肽组数据集（包含40361个独特肽段鉴定）进行了荟萃分析，并研究了HLA呈现的抗原图谱内的异同。我们发现癌症HLA肽组数据集沿着实体和谱系线特异性聚类，这表明免疫肽组直接反映了潜在（肿瘤）生物学的差异。与这些发现一致，我们仅检测到一小部分跨越实体的抗原，这些抗原在不同患者队列中的呈现频率主要较低。这些发现表明，用于治疗HM的T细胞免疫疗法的设计理想情况下应以实体特异性方式进行。
