Lebel-Binay S, Laguerre B, Quintin-Colonna F, Conjeaud H, Magazin M, Miloux B, Pecceu F, Caput D, Ferrara P, Fradelizi D
Laboratoire Immunomodulation et Autoimmunité, INSERM U283, Hôpital Cochin, Paris, France.
Eur J Immunol. 1995 Aug;25(8):2340-8. doi: 10.1002/eji.1830250833.
Cytokines locally delivered to the site of a tumor boost both specific and nonspecific host anti-tumor defenses. Interleukin (IL)-13 is a recently described cytokine produced by mouse type 2 helper T lymphocytes. The aim of this study was to evaluate the inhibition of tumor growth induced by IL-13 delivered locally within or around transplanted tumor cells in mice. We observed that local administration of IL-13 at the site of transplanted tumor cells in vivo had potent inhibitory effects on growth of both immunogenic (P815 mastocytoma, H-2d) or nonimmunogenic (3LL lung carcinoma, H-2b) tumor cells. Mice injected with transfected P815 cells secreting large amounts of IL-13 rejected the P815 tumor and developed systemic specific anti-tumor immunity leading to long-lasting specific anti-tumor protection. Less efficient anti-tumoral effects were obtained with the nonimmunogenic 3LL tumor model when local administration of IL-13 was achieved by co-inoculating xenogeneic chinese hamster ovary (CHO) IL-13 cells. Several local injections of CHO IL-13 cells were needed to obtain rejection of 3LL tumors and no induction of long-lasting anti-3LL memory was obtained. Several studies were performed to elucidate the IL-13 anti-tumoral effects. Experiments with nude mice indicated that Il-13 can also stimulate nonspecific anti-tumor defenses. The histological examination of P815 IL-13 cells undergoing rejection showed monocytic cells and neutrophils infiltrating the tumor. Studies indicated that IL-13 administered in vitro did not directly stimulate the cytotoxicity of peritoneal macrophages and natural killer cells. However, experiments with Boyden chemotaxis chambers indicated that IL-13 was chemotactic for macrophages. Finally, preliminary experiments in vitro suggest that IL-13 improved antigenic presentation of P815 membranes. Thus, anti-tumor effects of IL-13 in vivo most probably result from pleiotropic effects including recruitment of nonspecific cells and improved stimulation of immune-specific anti-tumor effectors.
局部递送至肿瘤部位的细胞因子可增强宿主特异性和非特异性抗肿瘤防御。白细胞介素（IL）-13是最近描述的由小鼠2型辅助性T淋巴细胞产生的细胞因子。本研究的目的是评估在小鼠移植肿瘤细胞内或其周围局部递送IL-13对肿瘤生长的抑制作用。我们观察到，在体内移植肿瘤细胞部位局部给予IL-13对免疫原性（P815肥大细胞瘤，H-2d）或非免疫原性（3LL肺癌，H-2b）肿瘤细胞的生长均有强大的抑制作用。注射分泌大量IL-13的转染P815细胞的小鼠排斥P815肿瘤，并产生全身特异性抗肿瘤免疫，从而导致持久的特异性抗肿瘤保护。当通过共接种异种中国仓鼠卵巢（CHO）IL-13细胞在局部给予IL-13时，非免疫原性3LL肿瘤模型获得的抗肿瘤效果较差。需要多次局部注射CHO IL-13细胞才能使3LL肿瘤被排斥，并且未诱导出持久的抗3LL记忆。进行了多项研究以阐明IL-13的抗肿瘤作用。对裸鼠进行的实验表明，IL-13还可刺激非特异性抗肿瘤防御。对正在发生排斥反应的P815 IL-13细胞进行组织学检查显示，单核细胞和中性粒细胞浸润肿瘤。研究表明，体外给予IL-13不会直接刺激腹膜巨噬细胞和自然杀伤细胞的细胞毒性。然而，使用博伊登趋化室进行的实验表明，IL-13对巨噬细胞具有趋化作用。最后，体外初步实验表明，IL-13可改善P815细胞膜的抗原呈递。因此，IL-13在体内的抗肿瘤作用很可能源于多效性作用，包括募集非特异性细胞以及改善对免疫特异性抗肿瘤效应器的刺激。
