Genetically regulated response to intravesical Bacillus Calmette Guerin immunotherapy of orthotopic murine bladder tumor
Genetically regulated response to intravesical Bacillus Calmette Guerin immunotherapy of orthotopic murine bladder tumor
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DOI：
10.1016/s0022-5347(01)64576-2
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发表时间：
1997-08-01
影响因子：
6.6
通讯作者：
Skamene, E
中科院分区：
文献类型：
--
作者：
Kadhim, SA;Chin, JL;Skamene, E
目的：在Bcg（r）和Bcg（s）近交系同类系小鼠中使用鼠膀胱肿瘤MM 45 T评估对膀胱内卡介苗（BCG）免疫疗法的遗传调节宿主应答。使用BALB/c（Bcg（s）等位基因）和BALB/c. CD 2（CD 2）（Bcg（r）等位基因）的磁共振成像（MRI）进行肿瘤检测和BCG治疗反应监测。原位植入MM 45 T肿瘤细胞的小鼠。膀胱内BCG滴注（每周3次，持续3周）用于预防Bcg（r）和Bcg（s）菌株的肿瘤植入，并作为MRI证实的已建立肿瘤的确定性治疗。植入两种未处理小鼠品系的肿瘤作为对照。膀胱内注射卡介苗也进行了建立异位皮下肿瘤在两个菌株。免疫反应在所有组进行了评估，通过流式细胞术分析膀胱冲洗液细胞成分，测量CD 4（+）（辅助/诱导）和CD 8（+）（细胞毒性/抑制）细胞subsets.Results：BCG到建立异位肿瘤病灶内注射显示生长抑制的BCG（S）株，但不是在BCG（R）株。膀胱内BCG治疗对建立原位肿瘤表现出显着的肿瘤消退的BCG（S）菌株相比，控制，但没有影响的BCG（R）strain.Conclusion：BCG的差异抗肿瘤活性的BCG（S）和BCG（R）同源小鼠菌株支持的概念，即卡介苗接种的Beg基因控制的反应决定，至少部分，宿主对免疫治疗的反应。这些结果对膀胱癌膀胱灌注治疗的患者选择具有潜在的临床意义。
Purpose: Genetically regulated host response to intravesical Bacillus Calmette Guerin (BCG) immunotherapy was assessed using the murine bladder tumor MM45T in Bcg(r) and Bcg(s) inbred congenic strains of mice.Materials and Methods: Tumor detection and monitoring of treatment response to BCG was carried out using magnetic resonance imaging (MRI) of BALB/c (Bcg(s) allele) and BALB/c.CD2 (CD2) (Bcg(r) allele) mice implanted orthotopically with MM45T tumor cells. Intravesical BCG instillation (3 doses per week for 3 weeks) was used as prophylaxis against tumor implantation in both Bcg(r) and Bcg(s) strains and as definitive treatment against MRI-confirmed established tumors. Tumors implanted in both strains of untreated mice served as controls. Intravesical injection of BCG was also performed in established heterotopic subcutaneous tumors in both strains. Immunologic response in all groups was assessed by flow cytometric analysis of the bladder irrigation fluid cell composition, measuring CD4(+) (helper/inducer) and CD8(+) (cytotoxic/suppressor) cell subsets.Results: Intralesional injection of BCG into established heterotopic tumors showed growth inhibition in the Bcg(s) strain but not in the Bcg(r) strain. Intravesical BCG treatment against established orthotopic tumors showed significant tumor regression in the Bcg(s) strain compared to control but there was no effect in the Bcg(r) strain.Conclusion: The differential anti-tumor activity of BCG in the Bcg(s) and Bcg(r) congenic murine strains supports the notion that Beg gene-controlled responsiveness to BCG innoculation determines, at least partially, the host response to immunotherapy. These results have potential clinical significance in patient selection for intravesical therapy for bladder cancer.