Immunophenotype Rearrangement in Response to Tumor Excision May Be Related to the Risk of Biochemical Recurrence in Prostate Cancer Patients

Paulius Bosas; Gintaras Zaleskis; Daiva Dabkevičiene; Neringa Dobrovolskiene; Agata Mlynska; Renatas Tikuišis; Albertas Ulys; Vita Pašukoniene; Sonata Jarmalaitė; Feliksas Jankevičius

doi:10.3390/jcm10163709

Immunophenotype Rearrangement in Response to Tumor Excision May Be Related to the Risk of Biochemical Recurrence in Prostate Cancer Patients

J Clin Med. 2021 Aug 20;10(16):3709. doi: 10.3390/jcm10163709.

Authors

Affiliations

¹ Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania.
² National Cancer Institute of Lithuania, 08406 Vilnius, Lithuania.
³ Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, 10223 Vilnius, Lithuania.
⁴ Life Sciences Center, Institute of Biosciences, Vilnius University, 10257 Vilnius, Lithuania.
⁵ Vilnius University Hospital Santaros Klinikos, 08661 Vilnius, Lithuania.

Abstract

Background: 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.

Methods: 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.

Results: 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^-1 (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 (p < 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, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 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 (p = 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 (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16).

Conclusion: 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.

Keywords: biochemical recurrence; immunophenotyping; prostate cancer; prostatectomy.