Jacobs Benedikt, Tognarelli Sara, Poller Kerstin, Bader Peter, Mackensen Andreas, Ullrich Evelyn
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Radiumhospital , Oslo , Norway ; The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo , Oslo , Norway ; Department of Haematology and Oncology, University Hospital Erlangen , Erlangen , Germany.
Department of Pediatric Stem Cell Transplantation and Immunology, Children's Hospital, Johann Wolfgang Goethe-University , Frankfurt , Germany ; LOEWE Center for Cell and Gene Therapy, Johann Wolfgang Goethe-University , Frankfurt , Germany.
Front Immunol. 2015 Nov 24;6:583. doi: 10.3389/fimmu.2015.00583. eCollection 2015.
High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56(++) NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56(++) NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.
大剂量化疗联合连续自体干细胞移植（autoSCT）是治疗恶性淋巴瘤或多发性骨髓瘤患者的一种成熟治疗方案。自然杀伤（NK）细胞是免疫监视的重要组成部分，自体干细胞移植后其细胞数量可预测无进展生存期和总生存期。为了增进对自体干细胞移植后NK细胞作用的了解，我们研究了接受自体干细胞移植治疗患者的不同NK细胞亚群、其表型及其功能。自体干细胞移植后白细胞再生（>1000个白细胞/μl）后，CD56(++)NK细胞是主要的NK细胞亚群。令人惊讶的是，与自体干细胞移植前或之后的时间点相比，这些细胞的CD57和杀伤细胞免疫球蛋白样受体（KIRs）表面表达水平异常高。此外，这些NK细胞强烈上调KIR2DL2/3/S2和KIR3DL1，而KIR2DL1/S1保持不变，表明这群细胞来自更不成熟的NK细胞而非活化的成熟NK细胞。值得注意的是，白细胞再生后早期，NK细胞在与肿瘤相互作用时就已经能够脱颗粒并产生IFN-γ和MIP-1β。总之，我们描述了自体干细胞移植后不久CD56(++)NK细胞上CD57和KIRs的异常上调。重要的是，这些NK细胞在这个早期时间点与肿瘤相互作用时功能正常。
