Department of Urology and Pediatric Urology, University Hospital Erlangen, FAU Erlangen-Nürnberg, 91054 Erlangen, Germany.
Institute of Pathology, University Hospital Erlangen, FAU Erlangen-Nürnberg, 91054 Erlangen, Germany.
Cells. 2021 Jan 15;10(1):159. doi: 10.3390/cells10010159.
Bladder cancer (BCa) is the tenth most commonly diagnosed malignant cancer worldwide. Although adjuvant chemotherapy following radical cystectomy is a common therapy for muscle invasive bladder cancer patients, no applicable biomarkers exist to predict which patients will benefit from chemotherapy. In this study, we examined three immune cell markers, the chemokine CC motif ligand 2 (CCL2), the pan macrophage marker cluster of differentiation 68 (CD68) and the M2 macrophage marker cluster of differentiation 163 (CD163), using immunohistochemistry to determine their predictive value for the chemotherapy response in different nodal stage (pN0 vs. pN1 + 2) and tumor stage subgroups (pT2 vs. pT3 + 4). The prognosis was studied in terms of the overall survival (OS), disease-specific survival (DSS), and recurrence-free-survival (RFS) in 168 muscle invasive BCa patients. Chemotherapy was associated with a poorer prognosis in patients with a higher expression of the immune markers CCL2 (RFS), CD68 (DSS and RFS), and CD163 (DSS and RFS) in the N0 group and with poorer survival in patients with a higher expression of the immune markers CCL2 (OS, DSS, and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS, DSS, and RFS) in the pT2 group when compared with treatments without chemotherapy. In contrast, chemotherapy was associated with a better prognosis in patients with a low expression of the immune markers CCL2 (DSS and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS) in the N1 + 2 group. In addition, chemotherapy was associated with improved survival in patients with a low expression of the immune marker CD68 (OS and DSS) and there was a trend for a better prognosis in patients with a low expression of CD163 (OS) in the pT3 + 4 group compared to patients not treated with chemotherapy. Interestingly, CD68 appeared to be the most applicable immune marker to stratify patients by the outcome of chemotherapy in the nodal stage and tumor stage groups. Overall, we suggest that, in addition to the clinical factors of tumor stage and nodal stage, it is also meaningful to consider the abundance of immune cells, such as macrophages, to better predict the response to chemotherapy for BCa patients after radical treatment.
膀胱癌（BCa）是全球第十大常见恶性肿瘤。尽管根治性膀胱切除术后辅助化疗是肌层浸润性膀胱癌患者的常见治疗方法，但目前尚无适用的生物标志物可预测哪些患者将从化疗中受益。在这项研究中，我们使用免疫组织化学检测了三种免疫细胞标志物，趋化因子 CC 基序配体 2（CCL2）、全巨噬细胞标志物分化群 68（CD68）和 M2 巨噬细胞标志物分化群 163（CD163），以确定它们在不同淋巴结分期（pN0 与 pN1 + 2）和肿瘤分期亚组（pT2 与 pT3 + 4）中对化疗反应的预测价值。在 168 例肌层浸润性膀胱癌患者中，根据总生存期（OS）、疾病特异性生存期（DSS）和无复发生存期（RFS）研究了预后。在 N0 组中，免疫标志物 CCL2（RFS）、CD68（DSS 和 RFS）和 CD163（DSS 和 RFS）表达较高的患者，以及在 pT2 组中，免疫标志物 CCL2（OS、DSS 和 RFS）、CD68（OS、DSS 和 RFS）和 CD163（OS、DSS 和 RFS）表达较高的患者，化疗与较差的预后相关，而与未接受化疗的患者相比，化疗与免疫标志物 CCL2（DSS 和 RFS）、CD68（OS、DSS 和 RFS）和 CD163（OS）表达较低的患者预后较好。此外，在 N1 + 2 组中，免疫标志物 CD68（OS、DSS 和 RFS）表达较低的患者化疗后生存得到改善，而在 pT3 + 4 组中，免疫标志物 CD163（OS）表达较低的患者有更好的预后趋势。有趣的是，与未接受化疗的患者相比，在淋巴结分期和肿瘤分期组中，CD68 似乎是分层患者化疗结果的最适用免疫标志物。总的来说，我们建议除了肿瘤分期和淋巴结分期的临床因素外，考虑巨噬细胞等免疫细胞的丰度也具有重要意义，以更好地预测肌层浸润性膀胱癌患者根治治疗后的化疗反应。
