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低剂量率近距离放射治疗前列腺癌的长期疗效及抗肿瘤免疫激活反应

Long-term outcome and antitumor immune activation response in prostate cancer treated with low-dose-rate brachytherapy.

作者信息

Wang Zengzeng, Wang Li, Zhang Qiang, Xu Yong, Zhang Changwen

机构信息

Department of Urology, Tianjin Beichen Traditional Chinese Medicine Hospital, Tianjin, China.

Department of Obstetrics, The Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Medicine (Baltimore). 2024 Nov 22;103(47):e40574. doi: 10.1097/MD.0000000000040574.

Abstract

To evaluate the long-term clinical outcomes of iodine-125 low dose-rate brachytherapy (LDR-BT)-based treatment approaches for ≤ cT3 prostate cancer (PC) patients in China, as well as the effects on the PC immune microenvironment. Data was retrospectively collected from 237 patients with ≤ cT3 PC who were treated with radical prostatectomy (RP) or LDR-BT alone or in combination with androgen deprivation therapy (ADT), and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS) and overall survival (OS) rates were compared. In 63 cases, PC patients received RP after biopsy, received at least 6 months of ADT before RP, or received LDR-BT and deferred limited transurethral resection of the prostate (TURP). Immunohistological analyses and expression comparisons of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs, expressing CD3, CD4, CD8, and PD-1) on tissue sections from archival prostate biopsy samples with corresponding TURP or RP history were performed by paired t test. The 8-year bPFS, PCSS, and OS rates for LDR-BT and RP were 53.4% and 63.6%, 84.9% and 86.8%, and 63.8% and 70.2%, respectively, although these differences were not statistically significant. PD-L1 was expressed in 35 of 63 cases. The average infiltration scores of TILs (expressing CD3, CD4, and CD8) were 3.6 (1-5), 2.90 (1-5), and 2.46 (1-5), respectively. PD-1 + T cells were seen in 55.6% of cases, with an average score of 0.89 (range: 0-3). In TURP tissue samples from 23 patients, CD3+, CD4+, and CD8 + T cells increased significantly. PD-1 + T cells exhibited a moderate increase, with conversion to positive PD-1 expression in T cells observed in 13 out of 14 cases. The PD-L1 expression score of PC cells was significantly elevated, with conversion to positive in 8 of 9 cases. LDR-BT monotherapy and combination therapy with external beam radiotherapy (EBRT) and ADT are suitable treatment approaches for low-risk and intermediate- or high-risk PC, respectively. Most TILs in PC are not tumor antigen-specific T-cells. LDR-BT can stimulate anti-tumor immunity during a narrow time window and should be combined with immunotherapy as an auxiliary therapy.

摘要

为了评估在中国将碘-125低剂量率近距离放射治疗(LDR-BT)作为治疗方法对≤cT3期前列腺癌(PC)患者的长期临床疗效,以及对PC免疫微环境的影响。回顾性收集了237例≤cT3期PC患者的数据,这些患者接受了根治性前列腺切除术(RP)、单独的LDR-BT或与雄激素剥夺治疗(ADT)联合治疗,并比较了生化无进展生存期(bPFS)、前列腺癌特异性生存期(PCSS)和总生存期(OS)率。在63例患者中,PC患者在活检后接受了RP,在RP前接受了至少6个月的ADT,或接受了LDR-BT并推迟了有限的经尿道前列腺切除术(TURP)。通过配对t检验对存档前列腺活检样本的组织切片上程序性死亡配体1(PD-L1)和肿瘤浸润淋巴细胞(TILs,表达CD3、CD4、CD8和PD-1)进行免疫组织学分析和表达比较。LDR-BT和RP的8年bPFS、PCSS和OS率分别为53.4%和63.6%、84.9%和86.8%、63.8%和70.2%,尽管这些差异无统计学意义。63例中有35例表达PD-L1。TILs(表达CD3、CD4和CD8)的平均浸润评分为3.6(1-5)、2.90(1-5)和2.46(1-5)。55.6%的病例中可见PD-1+T细胞,平均评分为0.89(范围:0-3)。在23例患者的TURP组织样本中,CD3+、CD4+和CD8+T细胞显著增加。PD-1+T细胞有中度增加,14例中有13例观察到T细胞中PD-1表达转为阳性。PC细胞的PD-L1表达评分显著升高,9例中有8例转为阳性。LDR-BT单一疗法以及与外照射放疗(EBRT)和ADT联合疗法分别适用于低风险和中或高风险PC。PC中的大多数TILs不是肿瘤抗原特异性T细胞。LDR-BT可在狭窄的时间窗内刺激抗肿瘤免疫,应与免疫疗法联合作为辅助治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ab/11596431/2cc243f5514f/medi-103-e40574-g001.jpg

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