Goswami Meghali, Prince Gabrielle, Biancotto Angelique, Moir Susan, Kardava Lela, Santich Brian H, Cheung Foo, Kotliarov Yuri, Chen Jinguo, Shi Rongye, Zhou Huizhi, Golding Hana, Manischewitz Jody, King Lisa, Kunz Lauren M, Noonan Kimberly, Borrello Ivan M, Smith B Douglas, Hourigan Christopher S
Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive Room 10CRC 5-5216, Bethesda, MD, 20814-1476, USA.
Johns Hopkins University, Baltimore, MD, USA.
J Transl Med. 2017 Jul 10;15(1):155. doi: 10.1186/s12967-017-1252-2.
Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy.
We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets.
Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy.
Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.
成人急性髓系白血病（AML）化疗后适应性免疫细胞的变化可能对免疫治疗的成功产生影响。本研究旨在确定完成化疗且可能成为免疫治疗候选者的成年AML患者免疫系统的功能能力。
我们将对季节性流感疫苗接种的反应作为免疫系统强健性的替代指标，对10例化疗后完全缓解的AML患者进行了检测，并对适应性免疫细胞亚群进行了基因、表型和功能特征分析。
只有2例患者接种疫苗后产生了保护性抗体滴度，大多数患者的过渡性和记忆性B细胞频率异常。B细胞受体测序显示，大多数患者的B细胞库几乎没有体细胞超突变的证据。相反，T细胞群体的频率与健康对照相似，细胞毒性T细胞在接种疫苗后表现出抗原特异性活性。在距离化疗时间最短的AML患者中，效应T细胞的程序性死亡蛋白1（PD-1）表达增加。
我们的结果表明，虽然细胞免疫的某些方面恢复迅速，但在AML强化细胞毒性化疗后的一年内，体液免疫并未完全重建。观察到的B细胞异常可能解释了AML患者化疗后对疫苗接种反应不佳的原因。此外，化疗后不久B细胞和T细胞免疫恢复的脱节以及PD-1表达增加可能对几种免疫治疗方式的成功产生影响。
