Grangeon Cendrine, Cormary Carine, Douin-Echinard Vickorine, Favre Gilles, Couderc Bettina, Tilkin-Mariamé Anne-Françoise
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA/UPRES 2048, Institut Claudius Regaud 20-24, rue du Pont Saint-Pierre, Toulouse Cedex 31052, France.
Cancer Gene Ther. 2002 Mar;9(3):282-8. doi: 10.1038/sj.cgt.7700439.
As they should enhance tumor-specific antigen presentation by dendritic cells, tumor cell lines genetically modified to express CD154 molecules have been used in an attempt to induce protective antitumor immunity. Two murine models were used: the major histocompatibility complex (MHC) class I negative melanoma B16F10 and the MHC class I positive mammary adenocarcinoma TS/A. CD154 or mock-transfected B16F10 or TS/A cells were injected subcutaneously into H-2-compatible B6D2 mice. CD154 expression by tumor cells induced a complete rejection (in the TS/A model) or a striking reduction (in the B16F10 model) of modified tumors growth, but also a significant protection against the growth of mock tumor cells injected simultaneously, either mixed with the CD154-expressing tumor cells, or in the other flank of mice. Thirty days after CD154-expressing tumor rejection, splenic lymphocytes from surviving tumor-free mice were able to inhibit tumor proliferation in vitro and significant amounts of IFN-gamma were detected in the sera of these mice. Growth kinetics of mock and CD154-expressing tumors in immunocompetent versus nude mice suggest that T lymphocytes and natural killer cells responses are implicated in this antitumor immunity. The injection of CD154-expressing tumor cell induced an antitumor protective response, both locally and distant from the injection site. The effect was most pronounced in MHC class I expressing TS/A tumor model.
由于它们应增强树突状细胞对肿瘤特异性抗原的呈递，因此已使用经过基因改造以表达CD154分子的肿瘤细胞系来诱导保护性抗肿瘤免疫。使用了两种小鼠模型：主要组织相容性复合体（MHC）I类阴性黑色素瘤B16F10和MHC I类阳性乳腺腺癌TS/A。将CD154或mock转染的B16F10或TS/A细胞皮下注射到与H-2相容的B6D2小鼠中。肿瘤细胞表达CD154可诱导修饰肿瘤生长完全被排斥（在TS/A模型中）或显著减少（在B16F10模型中），而且还对同时注射的mock肿瘤细胞的生长具有显著的保护作用，这些mock肿瘤细胞要么与表达CD154的肿瘤细胞混合，要么注射到小鼠的另一侧腹。在表达CD154的肿瘤被排斥30天后，无肿瘤存活小鼠的脾淋巴细胞能够在体外抑制肿瘤增殖，并且在这些小鼠的血清中检测到大量的IFN-γ。在免疫活性小鼠与裸鼠中mock肿瘤和表达CD154肿瘤的生长动力学表明，T淋巴细胞和自然杀伤细胞反应参与了这种抗肿瘤免疫。注射表达CD154的肿瘤细胞诱导了局部和远离注射部位的抗肿瘤保护反应。这种效应在表达MHC I类的TS/A肿瘤模型中最为明显。
