Vo Dang-Nghiem, Constantinides Michael, Allende-Vega Nerea, Alexia Catherine, Cartron Guillaume, Villalba Martin
IRMB, University Montpellier, INSERM, 34295 Montpellier, France.
IRMB, CHU Montpellier, 34295 Montpellier, France.
Vaccines (Basel). 2020 Dec 2;8(4):727. doi: 10.3390/vaccines8040727.
The lymphocyte lineage natural killer (NK) cell is part of the innate immune system and protects against pathogens and tumor cells. NK cells are the main cell effectors of the monoclonal antibodies (mAbs) that mediates antibody-dependent cell cytotoxicity (ADCC). Hence, it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. NK cells are heterogeneous with multiple subsets that may have specific activity against different attacks. The presence of viral-sculpted NK cell populations has already been described, but the presence of cancer-sculpted NK cells remains unknown. Cancer induces a broad NK cell dysfunction, which has not been linked to a specific population. Here, we investigated the NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and at least 30 days after treatment, which correlates with tumor cell clearance. We found that the NK lineage largely responded to the tumor by generating antitumor NK cells and renewing the population with a subset of immature NK cells. However, we failed to identify a specific "memory-like" subset with the NK cell markers used. Moreover, in patients in relapse, we found essentially the same NK populations as those found at diagnosis, suggesting that NK cells equally respond to the first or second tumor rise. Finally, we observed that previous cytomegalovirus (CMV) infection largely affects the tumor-associated changes in NK population, but the CMV-associated CD57NKG2C NK cell population does not appear to play any role in tumor immunity.
淋巴细胞谱系自然杀伤（NK）细胞是先天性免疫系统的一部分，可抵御病原体和肿瘤细胞。NK细胞是介导抗体依赖性细胞毒性（ADCC）的单克隆抗体（mAb）的主要细胞效应器。因此，了解NK细胞生理学和状态对于研究临床中mAb的生物学效应至关重要。NK细胞具有异质性，包含多个亚群，这些亚群可能对不同的攻击具有特定活性。病毒塑造的NK细胞群体已被描述，但癌症塑造的NK细胞群体是否存在仍不清楚。癌症会导致广泛的NK细胞功能障碍，这与特定亚群无关。在此，我们通过统一流形近似和投影（UMAP）嵌入图研究了霍奇金淋巴瘤（HL）和急性髓系白血病（AML）患者在诊断时以及治疗后至少30天的NK细胞群体，这与肿瘤细胞清除相关。我们发现，NK细胞谱系主要通过产生抗肿瘤NK细胞并以未成熟NK细胞亚群更新群体来对肿瘤作出反应。然而，我们未能用所使用的NK细胞标志物识别出特定的“记忆样”亚群。此外，在复发患者中，我们发现的NK细胞群体与诊断时基本相同，这表明NK细胞对首次或第二次肿瘤复发的反应相同。最后，我们观察到既往巨细胞病毒（CMV）感染在很大程度上影响NK细胞群体中与肿瘤相关的变化，但CMV相关的CD57NKG2C NK细胞群体似乎在肿瘤免疫中不起任何作用。
