Bosas Paulius, Zaleskis Gintaras, Dabkevičiene Daiva, Dobrovolskiene Neringa, Mlynska Agata, Tikuišis Renatas, Ulys Albertas, Pašukoniene Vita, Jarmalaitė Sonata, Jankevičius Feliksas
Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania.
National Cancer Institute of Lithuania, 08406 Vilnius, Lithuania.
J Clin Med. 2021 Aug 20;10(16):3709. doi: 10.3390/jcm10163709.
Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients.
Radical prostatectomy (RP) was performed on 108 PCa stage pT2-pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups.
The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = -2.0% d (AUC = 0.85 (95% CI, 0.78-0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 - CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL ( < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group ( < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients ( = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers ( = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset ( = 0.16).
Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.
已知前列腺癌（PCa）具有广泛的侵袭性和相对较高的免疫原性。本研究的目的是检查肿瘤切除对外周血免疫表型重排的影响，并阐明其是否与高危（HR）和低危（LR）患者的生化复发（BCR）相关。
对108例pT2 - pT3期PCa患者进行了根治性前列腺切除术（RP）。比较了LR组和HR组外周血术前与术后（1个月和3个月）的免疫表型谱（T细胞和B细胞亚群、髓系来源的抑制性细胞（MDSC）、自然杀伤细胞（NK）和调节性T细胞群体）。
HR组和LR组的无BCR生存期差异显著。术后前列腺特异性抗原（PSA）衰减率（定义为ePSA）在HR组明显较慢，在截断水平ePSA = -2.0% d时可预测BCR（曲线下面积（AUC） = 0.85（95%可信区间，0.78 - 0.90））。肿瘤切除后3个月，LR组自然杀伤细胞CD3 - CD16 + CD56 +细胞从232个/μL恢复至317个/μL（P < 0.05），而HR组未检测到这种变化。前列腺切除术还导致LR组CD8 +群体增加，主要是由于CD8 + CD69 +亚群（从术前的186个/μL增加至术后3个月的196个/μL，P < 0.01）。HR组存在CD8 + CD69 +亚群增加而总T细胞未增加的情况（P < 0.001）。肿瘤切除导致HR组髓系来源的抑制性细胞（MDSC）数量从12.4个/μL增加至16.2个/μL，而LR患者未检测到变化（P = 0.12）。术后恢复的免疫特征更可能出现在接受腹腔镜根治性前列腺切除术（LRP）的患者中。开放性RP（ORP）与MDSC数量增加相关（P = 0.002），而LRP的特征是免疫保留谱，MDSC亚群无变化（P = 0.16）。
前列腺癌患者的肿瘤切除导致两种不同的免疫表型重排模式。低危组反应强烈，显示术后T细胞、NK细胞以及CD8 + CD69 +数量恢复，且抑制性MDSC未增加。高危组反应有限，伴有抑制性MDSC增加和CD8 + CD69 +增加。与ORP不同，腹腔镜手术方法在术后未导致MDSC增加。
