Ayari Cherifa, LaRue Hélène, Hovington Hélène, Decobert Marc, Harel François, Bergeron Alain, Têtu Bernard, Lacombe Louis, Fradet Yves
Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, CHUQ, Québec, Canada.
Eur Urol. 2009 Jun;55(6):1386-95. doi: 10.1016/j.eururo.2009.01.040. Epub 2009 Feb 3.
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.
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.
Patients were treated by transurethral resection followed by maintenance BCG.
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.
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).
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.
肿瘤浸润性树突状细胞（TIDCs）和肿瘤相关巨噬细胞（TAMs）作为免疫反应标志物的临床意义已在多种癌症中得到报道。
在卡介苗（BCG）免疫治疗前，检测非肌层浸润性尿路上皮癌（NMIUC）中CD83(+)树突状细胞（DCs）和CD68(+)巨噬细胞的肿瘤浸润情况，并评估它们在免疫治疗反应中的意义。
设计、场所和参与者：招募有高复发和进展风险的NMIUC患者进行BCG反应标志物的研究。
患者接受经尿道切除术，随后进行维持性BCG治疗。
在BCG治疗前，分别对53例和46例NMIUC肿瘤进行抗CD83和抗CD68单克隆抗体的免疫组织化学染色。根据乳头轴、基质、淋巴聚集物内阳性细胞的平均密度以及肿瘤浸润情况计算评分指数。
CD83(+) TIDCs主要在淋巴聚集物中观察到。多因素Cox回归分析显示，维持性BCG（超过一个维持周期）对切除时CD83(+) TIDCs水平低的患者非常有效（风险比[HR]：0.035；p = 0.002），但对CD83(+) TIDCs水平高的患者疗效降低（HR：0.87；p = 0.810）。CD83(+) TIDCs的高水平浸润在接受一个或不接受维持性BCG周期治疗的患者中略微降低了复发风险（HR：0.4；p = 0.117）。在同一人群中，CD68(+) TAMs的强烈浸润与复发风险增加相关（HR：3.8；p = 0.013）。
这些结果表明，CD83(+) TIDCs或CD68(+) TAMs浸润水平高的患者对BCG免疫治疗的反应不佳。如果在更大的队列中得到证实，这些细胞的预处理浸润水平可能有助于影响治疗策略的选择。
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