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

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.

Avaliação da Expressão das Células NK no Câncer de Próstata após Prostatectomia Radical

“…Apenas 3 artigos realizaram análises de sobrevida e/ou estudos de correlação entre as células NK e a recorrência bioquímica. [8][9][10] Três artigos também descreveram valores de PSA, mas em apenas um deles houve análise pormenorizada, estabelecendo correlação entre a população das células NK e/ou sua atividade e fatores prognósticos já utilizados na prática clínica como escore de Gleason e estadio TNM.9…”

“…de sua atividade como fator prognóstico. [8][9][10][11][12] Com exceção do trabalho de Bosas e colaboradores, foi demonstrado aumento da população das células NK ou de sua atividade após PTR e uma correlação positiva entre aumento da população de células NK pós-operatória ou da sua expressão e aumento da sobrevida livre de doença/recidiva bioquímica.…”

Boosting the Immune Response—Combining Local and Immune Therapy for Prostate Cancer Treatment

“…Their functions include the inhibition of CLTs through various mechanisms (e.g., producing reactive oxygen species (ROS) or interactions with the T cell receptor [TCR]), suppressing natural killer (NK) cells, and Tregs induction [ 56 , 57 , 58 , 59 , 60 ]. The level of MDSCs correlates with the stage of PC and applied treatment, as well as with the serum levels of crucial inflammatory mediators—IL-6 and IL-8 [ 61 , 62 , 63 ].…”

Current Trends in Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Disease from Appendiceal and Colorectal Malignancies

“…CRS has itself been proposed to be a form of immunotherapy [ 208 ]. Subsequent studies have confirmed that tumor resection can re-activate the native immune system to an anti-tumor phenotype [ 209 , 210 , 211 ]. In fact, catumaxomab, a trifunctional antibody, was approved in Europe for intraperitoneal use to treat malignant ascites, has demonstrated promise to directly treat GI-derived PC, and is undergoing additional evaluation of efficacy for curative intent (NCT04222114, NCT01815528, and NCT01246440) [ 212 , 213 , 214 , 215 , 216 ].…”