Chu Christina S, Woo Edward Y, Toll Alanna J, Rubin Stephen C, June Carl H, Carroll Richard G, Schlienger Katia
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Clin Immunol. 2002 Mar;102(3):291-301. doi: 10.1006/clim.2001.5179.
We have generated dendritic cells (DCs) from tumor-associated macrophages (TAMs) obtained from ascites fluid or tumor specimens of ovarian cancer patients, and compared them phenotypically and functionally to DCs derived from the patients' peripheral blood mononuclear cells (PBMCs). Both immature and mature DCs could be generated from TAMs. However, TAM-derived DCs underwent maturation to a lesser degree than PBMC-derived DCs, as measured by DC receptor surface expression. Nonetheless, in allogeneic mixed lymphocyte reactions, TAM-derived DCs stimulated T cell proliferation as efficiently as PBMC-derived DCs. In addition, TAM-derived DCs presenting tumor Ags were capable of stimulating IFN-gamma secretion by tumor-specific T cell lines. Thus, TAMs isolated from ovarian cancer patients can be used to generate significant numbers of DCs. Therefore, TAMs have potential use for either ex vivo or in vivo DC-based immunotherapy, particularly in individuals in which more conventional sources of DCs have been depleted.
我们从卵巢癌患者的腹水或肿瘤标本中获取肿瘤相关巨噬细胞(TAM),并将其诱导分化为树突状细胞(DC),然后在表型和功能上与从患者外周血单个核细胞(PBMC)中获得的DC进行比较。TAM可产生未成熟和成熟的DC。然而,通过DC受体表面表达检测发现,TAM来源的DC成熟程度低于PBMC来源的DC。尽管如此,在同种异体混合淋巴细胞反应中,TAM来源的DC刺激T细胞增殖的效率与PBMC来源的DC相同。此外,呈递肿瘤抗原的TAM来源的DC能够刺激肿瘤特异性T细胞系分泌γ干扰素。因此,从卵巢癌患者中分离出的TAM可用于产生大量DC。所以,TAM在基于DC的体外或体内免疫治疗中具有潜在用途,尤其是在那些更传统的DC来源已耗竭的个体中。