Bladder Tumor Infiltrating Mature Dendritic Cells and Macrophages as Predictors of Response to Bacillus Calmette-Guérin Immunotherapy

详细信息    查看全文

• 作者：Cherifa Ayari ; Hé ; lè ; ne LaRue ; Hé ; lè ; ne Hovington ; Marc Decobert ; Franç ; ois Harel ; Alain Bergeron ; Bernard Tê ; tu ; Louis Lacombe ; Yves Fradet
• 关键词：BCG immunotherapy ; Non-muscle-invasive bladder cancer ; Prognosis ; Tumor-associated macrophages ; Tumor-infiltrating dendritic cells
• 刊名：European Urology
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：55
• 期：6
• 页码：1386-1396
• 全文大小：714 K

文摘

Background

The clinical significance of tumor-infiltrating dendritic cells (TIDCs) and tumor-associated macrophages (TAMs) as markers of immune response has been reported for many cancers.

Objective

To measure tumor infiltration by CD83⁺ dendritic cells (DCs) and CD68⁺ macrophages in non–muscle-invasive urothelial cancer (NMIUC) prior to bacillus Calmette-Guérin (BCG) immunotherapy and to evaluate their significance in the response to immunotherapy.

Design, setting, and participants

Patients with NMIUC at high risk of recurrence and progression were recruited for a study on markers of the response to BCG.

Intervention

Patients were treated by transurethral resection followed by maintenance BCG.

Measurements

Immunohistochemical staining with anti-CD83 and anti-CD68 monoclonal antibodies on 53 and 46 NMIUC tumors, respectively, prior to BCG treatment. A scoring index was calculated based on the average density of positive cells within the papillary axis, the stroma, lymphoid aggregates, and infiltration into tumors.

Results and limitations

CD83⁺ TIDCs were observed mostly within lymphoid aggregates. Multivariate Cox regression analysis showed that maintenance BCG (more than one maintenance cycle) was highly effective in patients with a low level of CD83⁺ TIDCs at time of resection (hazard ratio [HR]: 0.035; p = 0.002) but showed reduced efficacy in patients with a high level of CD83⁺ TIDCs (HR: 0.87; p = 0.810). A high level of infiltration by CD83⁺ TIDCs slightly decreased the risk of recurrence in patients treated with one or no maintenance BCG cycle (HR: 0.4; p = 0.117). In the same population, a strong infiltration of CD68⁺ TAMs was associated with an increased risk of recurrence (HR: 3.8; p = 0.013).

Conclusions

These results suggest that patients with a high level of infiltration by CD83⁺ TIDCs or CD68⁺ TAMs do not respond as well to BCG immunotherapy. If confirmed in larger cohorts, the pretreatment level of infiltration by these cells may be useful to influence the choice of treatment strategy.