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.

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor (AR) genes—for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers. In particular, the combination of sPD-L1, sPD-1, and AR demonstrated the most significant improvement in diagnostic performance, increasing the area under the curve (AUC) from 0.65 to 0.81 and sensitivity from 60% to 88%, compared to AR alone. PSMA demonstrated an AUC of 0.82 and a specificity of 52.8%, which improved to an AUC of 0.85 and a specificity of 94.4% with the inclusion of sPD-L1 and sPD-1. Similarly, PCA3 achieved an AUC of 0.75 and a specificity of 53.8%, increasing to an AUC of 0.78 and a specificity of 76.9% when combined with these biomarkers. Incorporating sPD-L1 into a three-gene panel further elevated the AUC from 0.74 to 0.94. These findings underscore the value of multimodal liquid-based diagnostic panels in improving the management of clinically significant PCa.

Objectives: To assess the role of soluble PD-L1 and PD-1 in combination with mRNA transcripts of PCA3, PSMA, AR genes in diagnostics of clinically significant prostate cancer (PCa). Methods: For 68 PCa patients, plasma sPD-L1 and sPD-1 were measured by ELISA method and the urinary PSMA, PCA3 and AR were tested using RT-qPCR. Results: PSMA and AR were iden-tified as the most reliable biomarkers for predicting clinically significant prostate cancer, with AUCs of 0.81 and 0.78, respectively. Additionally, the expression levels of PSMA and PCA3 were associated with the pT3 stage. Despite the diagnostic potential of mRNA transcripts alone, the ad-dition of sPD-L1 and sPD-1 significantly enhanced diagnostic accuracy. Combination doubled the specificity of PCA3 from 44.1% to 88.0%, compared to PCA3 alone. sPD-L1, sPD-1 and AR resulted in the best distinction between clinically significant and insignificant prostate cancer, achieving an AUC of 0.97, an accuracy of 0.95, a sensitivity of 100%, a specificity of 95%, revealing the potential of AR in distinguishing clinically significant PCa, more effectively than PSMA and PCA3. Our find-ings highlight the significant potential of sPD-1 in enhancing diagnostic accuracy when added to a triple gene panel, achieving an AUC of 0.90 compared to an AUC of 0.78 without sPD-1. This un-derscores the value of sPD-1, which has been less explored than sPD-L1 in cancer diagnostics. Con-clusions: sPD-L1 and sPD-1 has a potential to significantly enhance the accuracy of PCa diagnostics when added to the diagnostic panel, alongside PSMA, PCA3, and AR mRNA transcripts.

Immunological differences between open and laparoscopic radical prostatectomies