Joseph-Pietras Debora, Carlier Annie, Madoulet Claudie, Albert Philippe
Laboratoire de Biologie Cellulaire and Moléculaire, EA 3796, U.F.R. des Sciences Exactes et Naturelles, Moulin de la Housse, BP 1039, 51687 Reims 2, France.
Anticancer Res. 2007 Nov-Dec;27(6B):3865-74.
Peripheral blood mononuclear cells (PBMCs) present an antitumor activity in vitro on doxorubicin-resistant B16 melanoma (B16R) spheroids, but do not inhibit tumor growth in vivo. This study aimed to improve in vivo the antitumor immune response by using antigen presenting cells.
After injection of B16R cells, mice received either tumor cell lysate-pulsed PBMCs, or naive or cytostatic tumor cell-pulsed bone marrow-derived dendritic cells (DCs). Tumor development and mouse survival were followed and spleen cell cytotoxic activity against B16R was estimated in vitro by Lactate dehydrogenase activity measurement.
The best results were obtained with peritumoral injections of cytostatic tumor cell-pulsed DCs which induced tumor regression, increased mouse survival and exhibited a higher splenocyte cytotoxic activity against B16R cells. When injected at a distant site, the efficacy was reduced. Furthermore, preventative injections of pulsed DCs induced protection of mice against B16R cells.
These results show the important role of cytostatic tumor cell-pulsed DCs in a specific antitumor immunity establishment. Consequently, they could be used combined with other treatments to improve clinical outcomes.
外周血单个核细胞（PBMCs）在体外对阿霉素耐药的B16黑色素瘤（B16R）球体具有抗肿瘤活性，但在体内并不抑制肿瘤生长。本研究旨在通过使用抗原呈递细胞在体内增强抗肿瘤免疫反应。
注射B16R细胞后，小鼠接受肿瘤细胞裂解物脉冲处理的PBMCs，或未处理的或经细胞抑制性肿瘤细胞脉冲处理的骨髓来源树突状细胞（DCs）。跟踪肿瘤发展和小鼠存活情况，并通过乳酸脱氢酶活性测量在体外评估脾细胞对B16R的细胞毒性活性。
瘤周注射经细胞抑制性肿瘤细胞脉冲处理的DCs取得了最佳效果，其诱导了肿瘤消退，提高了小鼠存活率，并对B16R细胞表现出更高的脾细胞细胞毒性活性。当在远处部位注射时，疗效降低。此外，预防性注射脉冲处理的DCs可诱导小鼠对B16R细胞产生保护作用。
这些结果表明经细胞抑制性肿瘤细胞脉冲处理的DCs在建立特异性抗肿瘤免疫中起重要作用。因此，它们可与其他治疗方法联合使用以改善临床疗效。
