Tumor-infiltrating lymphocytes (TILs) and the derived immunoscore (IS) have gained considerable attention over the last decade as prognostic markers in many solid cancers. However, in bladder cancer (BC), their prognostic value is not clearly established. The present study aimed to quantify the TILs rates in BC, assess the derived immunoscore, and investigate their prognostic value. An immunochemistry-based quantification of the different subtypes of TILS was performed on paraffin-embedded blocks from patients with invasive urothelial carcinoma of the bladder. We have assessed the rates of TILs, respectively, on peri-tumoral (PT) and intra-tumoral (IT) areas and calculated for each case the corresponding IS which is the index: CD8+/CD3+ TILs. The IS was then classified as low (I0, I1) or high (I2, I3, I4). We included 30 cases in the analysis. The median age of patients was 65 years with a sex ratio of 9. TILs densities and distribution were significantly variable between IT and PT areas CD3+ (p = 0.03) and CD8+ (p = 0.004) with the highest rates on the PT areas. In univariate analysis, a low density of CD8+ TILs was significantly associated with an advanced age (p = 0.05), with the presence of lympho-vascular invasion (p = 0.02) and with the absence of specific histological subtype (p = 0.05). A low immunoscore was significantly associated with the presence of lympho-vascular invasion (p = 0.004). No significant association was found between TILs subpopulations, the IS, and the other clinicopathological and survival data. The overall survival (OS) and disease-free survival (DFS) medians were slightly superior in highly T (CD3+/CD8+)-cell infiltrated tumors as well as tumors with a high IS densities. However, the univariate analysis showed that TILs and immunoscore did not impact overall survival (OS) and disease-free survival (DFS). TILs and immunoscore might be effective prognostic tools in BC. However, standardized quantification methods and further investigation on larger samples are highly recommended to definitively attest the prognostic value of TILs and IS in BC.

中文翻译：

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基于免疫化学的肿瘤浸润淋巴细胞定量和免疫评分作为膀胱癌的预后生物标志物

肿瘤浸润淋巴细胞 (TIL) 和衍生免疫评分 (IS) 作为许多实体癌的预后标志物在过去十年中受到了相当大的关注。然而，在膀胱癌（BC）中，它们的预后价值尚未明确确定。本研究旨在量化 BC 中的 TIL 率，评估衍生的免疫评分，并研究其预后价值。对膀胱浸润性尿路上皮癌患者的石蜡包埋块进行了基于免疫化学的不同亚型 TILS 的定量。我们分别评估了肿瘤周围 (PT) 和肿瘤内 (IT) 区域的 TIL 率，并为每种情况计算了相应的 IS，即指数：CD8+/CD3+ TIL。然后将 IS 分类为低（I0、I1）或高（I2、I3、I4）。我们在分析中纳入了 30 个案例。患者的中位年龄为 65 岁，性别比例为 9。IT 区和 PT 区 CD3+ (p = 0.03) 和 CD8+ (p = 0.004) 之间的 TIL 密度和分布差异显着，PT 区的比率最高。在单变量分析中，低密度的 CD8+ TIL 与高龄 (p = 0.05)、淋巴血管侵犯的存在 (p = 0.02) 以及特定组织学亚型的缺乏 (p = 0.05) 显着相关。低免疫评分与淋巴血管侵犯的存在显着相关（p = 0.004）。 TIL 亚群、IS 和其他临床病理学和生存数据之间没有发现显着关联。 T (CD3+/CD8+) 细胞高度浸润的肿瘤以及 IS 密度高的肿瘤的总生存期 (OS) 和无病生存期 (DFS) 中位数稍好。然而，单变量分析显示 TIL 和免疫评分不会影响总生存期 (OS) 和无病生存期 (DFS)。 TIL 和免疫评分可能是 BC 的有效预后工具。然而，强烈建议采用标准化量化方法和对更大样本进行进一步研究，以明确证明 TIL 和 IS 在 BC 中的预后价值。