Son Y I, Mailliard R B, Watkins S C, Lotze M T
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A.
Laryngoscope. 2001 Aug;111(8):1472-8. doi: 10.1097/00005537-200108000-00026.
Dendritic cells, the most potent of the antigen-presenting cells, have been widely studied as a promising tool for antitumor immunotherapies. However, little has been determined about the efficacy of dendritic cell-based therapy for the treatment of squamous cell carcinoma (SCC) because there are no known SCC-specific antigens. Recent reports indicate that dendritic cells can acquire antigens in the form of apoptotic cells and induce cytotoxic T-lymphocyte responses. The aim of this study was to test the feasibility of adoptive dendritic cell immunotherapy against SCC by using apoptotic tumor cells as a source of tumor antigens.
A poorly immunogenic SCC line KLN 205 was used to make subcutaneous tumors on the flank of DBA2/J syngeneic mice. Bone marrow-derived dendritic cells were pulsed with ultraviolet B-irradiated (apoptotic) KLN 205 cells in vitro and transferred to the opposite flank subcutaneously. Some of the animals received simultaneous intraperitoneal injections of low-dose interleukin-2.
When combined with interleukin-2, adoptive transfers of dendritic cells that were pulsed with apoptotic SCC significantly suppressed the tumor growth (P <.001) without notable side effects. Splenic T cells of treated mice produced greater amounts of interferon-gamma when restimulated with the relevant tumor (P <.001) as compared with control groups, indicative of an effective T-cell-mediated systemic immune response.
Adoptive transfer of dendritic cells pulsed with apoptotic tumor cells as a source of tumor antigens, can elicit effective antitumor responses in the poorly immunogenic SCC model when combined with interleukin-2.
树突状细胞是最强大的抗原呈递细胞,作为一种有前景的抗肿瘤免疫治疗工具已得到广泛研究。然而,由于不存在已知的鳞状细胞癌(SCC)特异性抗原,关于基于树突状细胞的疗法治疗SCC的疗效鲜为人知。最近的报告表明,树突状细胞能够以凋亡细胞的形式获取抗原并诱导细胞毒性T淋巴细胞反应。本研究的目的是通过使用凋亡肿瘤细胞作为肿瘤抗原来源,测试过继性树突状细胞免疫疗法治疗SCC的可行性。
使用免疫原性差的SCC细胞系KLN 205在同基因DBA2/J小鼠的胁腹制备皮下肿瘤。体外将紫外线B照射(凋亡)的KLN 205细胞脉冲加载到骨髓来源的树突状细胞上,然后皮下转移至对侧胁腹。部分动物同时腹腔注射低剂量白细胞介素-2。
当与白细胞介素-2联合使用时,用凋亡SCC脉冲加载的树突状细胞过继性转移可显著抑制肿瘤生长(P<.001),且无明显副作用。与对照组相比,经治疗小鼠的脾T细胞在用相关肿瘤再次刺激时产生更多的干扰素-γ(P<.001),表明存在有效的T细胞介导的全身免疫反应。
以凋亡肿瘤细胞作为肿瘤抗原来源脉冲加载的树突状细胞过继性转移,在与白细胞介素-2联合使用时,可在免疫原性差的SCC模型中引发有效的抗肿瘤反应。