肿瘤内 CD8+T 细胞浸润与接受根治性前列腺切除术的前列腺癌患者的生存改善相关。
High intratumoral CD8 T-cell infiltration is associated with improved survival in prostate cancer patients undergoing radical prostatectomy.
机构信息
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
出版信息
Prostate. 2021 Jan;81(1):20-28. doi: 10.1002/pros.24068. Epub 2020 Oct 21.
BACKGROUND
A high density of CD8 tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8 TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8 TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.
METHODS
Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8 cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8 TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a "minimal p value approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8 TIL density groups.
RESULTS
One hundred and forty-nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow-up time was 8.4 years. High CD8 TIL density was associated with improved 5-year overall survival (98% vs. 91%, p = .01) and prostate cancer-specific survival (99% vs. 95%, p = .04) compared with patients with low CD8 TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8 TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8 TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17-0.87; p = .02). In contrast to the prognostic value of CD8 TIL density, the CD8 cell density in the matched normal prostate tissue was not associated with any clinical outcomes.
CONCLUSION
Intratumoral CD8 T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8 cytotoxic T-cell infiltration may be beneficial for this population.
背景
在多种癌症中，高密集度的 CD8 肿瘤浸润淋巴细胞（TILs）与改善生存相关，但它在前列腺癌中的预后作用仍存在争议。我们的研究旨在评估前列腺癌患者接受根治性前列腺切除术（RP）时 CD8 TIL 的预后价值。我们假设 RP 标本中 CD8 TIL 的密度升高与改善的临床结局相关。这些信息可能有助于未来的免疫治疗临床试验设计和治疗选择。
方法
回顾性分析了 2006 年至 2012 年在罗切斯特大学帕克综合癌症中心接受 RP 的 230 例局限性前列腺癌患者的肿瘤微阵列，使用免疫组织化学进行分析。使用计算机评分系统评估 CD8 细胞密度。将队列按 CD8 TIL 密度的第 25 百分位数（即低 <四分位数 1 和高 ≥四分位数 1）进行分组。四分位数 1 阈值是通过基于总体生存的“最小 p 值方法”选择的，并用显著性校正进行了调整，以校正多重检验。比较了高 CD8 TIL 密度组与低 CD8 TIL 密度组的临床结局。
结果
149 例（65%）患者患有高危疾病（Gleason>7 或 pT3/4）。中位随访时间为 8.4 年。与低 CD8 TIL 密度组相比，高 CD8 TIL 密度组的 5 年总生存率（98% vs. 91%，p=0.01）和前列腺癌特异性生存率（99% vs. 95%，p=0.04）更高。高 CD8 TIL 密度组的 5 年生化无复发生存率和无转移生存率也有升高趋势（分别为 52% vs. 38%和 86% vs. 73%），尽管差异未达到统计学意义（p=0.18 和 p=0.05）。在多变量分析中，高 CD8 TIL 密度是总生存的独立有利预后因素（风险比=0.38；95%置信区间：0.17-0.87；p=0.02）。与 CD8 TIL 密度的预后价值相反，RP 标本中匹配的正常前列腺组织中的 CD8 细胞密度与任何临床结局均无关。
结论
在这一高危前列腺癌队列中，RP 标本中的肿瘤内 CD8 T 细胞浸润与 RP 后生存的改善独立相关。在 RP 前进行促进肿瘤内 CD8 细胞毒性 T 细胞浸润的免疫调节可能对这部分人群有益。
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