Vujanovic N L, Yasumura S, Hirabayashi H, Lin W C, Watkins S, Herberman R B, Whiteside T L
Department of Pathology, University of Pittsburgh School of Medicine, PA.
J Immunol. 1995 Jan 1;154(1):281-9.
Human NK cells can be separated into two functionally distinct subpopulations based on the ability to rapidly respond to IL-2 by adherence to solid surfaces. To determine functions of the NK cell subsets in solid tumor tissues, adherent (A) and nonadherent (NA) NK cells were evaluated for their ability to infiltrate multicellular tumor spheroids in vitro, to kill carcinoma (CA) cell targets in these spheroids, and to mediate antitumor activity in vivo. A-NK cells were less cytolytic than NA-NK cells against CA targets in single cell suspensions or in monolayers. However, A-NK cells showed a significantly better ability than NA-NK cells to infiltrate tumor tissues and kill tumor cells in spheroids of human squamous cell CA of the head and neck or breast CA. Perilesional delivery of human A-NK cells and IL-2 resulted in regression of established human squamous cell carcinoma of the head and neck tumors growing subcutaneously in immunosuppressed nude mice. Similarly, in a xenograft model of human gastric CA metastatic to liver of nude mice, a single intrasplenic injection of A-NK cells in combination with i.p. infusions of IL-2 significantly reduced the number of established hepatic metastases (p < 0.007) and prolonged survival of the mice (p < 0.003). In contrast, NA-NK cells were ineffective in either of the in vivo xenograft tumor models. These findings demonstrate that A-NK cells represent a biologically unique and important subset of NK cells that, in contrast to the rest of NK cells, function as effector cells in solid tumor tissues and, consequently, have a great antitumor therapeutic potential.
人类自然杀伤（NK）细胞可根据其通过黏附于固体表面对白细胞介素-2（IL-2）快速反应的能力，分为两个功能不同的亚群。为了确定NK细胞亚群在实体瘤组织中的功能，对贴壁（A）和非贴壁（NA）NK细胞进行了评估，检测它们在体外浸润多细胞肿瘤球体的能力、杀伤这些球体中癌细胞（CA）靶标的能力以及在体内介导抗肿瘤活性的能力。在单细胞悬液或单层培养中，A-NK细胞对CA靶标的细胞毒性低于NA-NK细胞。然而，在人头部和颈部鳞状细胞CA或乳腺CA的球体中，A-NK细胞浸润肿瘤组织和杀伤肿瘤细胞的能力明显优于NA-NK细胞。在免疫抑制的裸鼠皮下生长的人头部和颈部已建立的鳞状细胞癌肿瘤周围递送人A-NK细胞和IL-2，导致肿瘤消退。同样，在人胃癌转移至裸鼠肝脏的异种移植模型中，单次脾内注射A-NK细胞并腹腔内输注IL-2，显著减少了已建立的肝转移灶数量（p<0.007），并延长了小鼠的生存期（p<0.003）。相比之下，NA-NK细胞在这两种体内异种移植肿瘤模型中均无效。这些发现表明，A-NK细胞代表了NK细胞中一个生物学上独特且重要的亚群，与其他NK细胞不同，它们在实体瘤组织中作为效应细胞发挥作用，因此具有巨大的抗肿瘤治疗潜力。
