PDF(Pubmed)
Abstract：
The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients\' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.
摘要：
自然杀伤（NK）细胞的短命性质和异质性限制了基于NK细胞的疗法的发展。尽管它们被证明具有抗癌的安全性和有效性。这里,我们描述了生物学基础，长寿命抗肿瘤人NK细胞（CD56highCD16+）的详细表型和功能，在没有细胞分选或饲养细胞的情况下获得，在用卡介苗（BCG）引发外周血细胞后。Further,我们证明了细胞因子组合的存活剂量，不包括IL18，每周给予BCG引发的NK细胞，避免先天淋巴细胞耗尽，并导致先天细胞的特定长期增殖，对广泛的实体瘤发挥有效的细胞毒性功能，主要通过NKG2D。引人注目的是，在BCG和细胞因子刺激后，NKG2C+CD57-FcεRIγ+NK细胞群扩增，独立于HCMV血清学。这一策略被用来拯救抗肿瘤NK细胞，甚至来自癌症患者骨髓的抑制环境。证明BCG赋予NK细胞持久的抗肿瘤特征。
