Immunoprofiling: A prospective multi-cohort study to characterize circulating immune response in advanced prostate cancer.

e17055 Background: The tumor immune microenvironment (TIME) is a critical determinant of therapeutic response and resistance mechanisms in prostate cancer (PC). Understanding the composition and dynamics of immune cell populations within the TIME and peripheral blood may uncover novel prognostic and predictive biomarkers. This study aims to characterize the immune phenotype, including high-risk localized PC, metastatic hormone-sensitive prostate cancer (mHSPC), and castration-resistant prostate cancer (CRPC). Methods: This prospective multi-cohort study, initiated in September 2021, included three cohorts: high-risk localized PC, mHSPC, and CRPC. A 47-immune subpopulation panel (Table 1) was developed, and peripheral blood samples were collected at baseline, during treatment, and at disease progression. Immune phenotyping was performed via flow cytometry, with data analyzed using FlowJo software. The study received institutional ethics approval, and univariate and multivariate analyses were used to compare immune profiles between the mHSPC and CRPC cohorts. Results: A total of 49 patients (pts) were recruited: 34 mHSPC and 15 CPRC. Baseline blood samples were collected from all participants, and 82% also had samples taken prior to cycle 3 of standard therapy. Thirty-one of 49 pts received androgen receptor targeted therapies (ARTA) while 12 of 49 received chemotherapy. The median age at diagnosis was 72 years (range 52-91). Twenty-eight of 49 pts had a Gleason score ≥ 8, and 21 of 49 were diagnosed with metastatic de novo, with bone metastases (mts) being the most frequent site (45% with only bone mts, 27% with nodal and bone mts, 24% with only nodal mts, and 4.1% with visceral mts). Statistically significant differences were observed in the CD3+CD8+CXCR4+ and CD3+CD8+PSGL1+ subpopulations, showing higher levels in CRPC compared to mHSPC after treatment (95% CI [0.03, 0.26]; p=0.019 and p=0.04, respectively). NK cells CD56-KIR+ were significantly lower in CRPC compared to mHSPC, with a significant reduction observed post-therapy in CRPC (p<0.01) in the multivariate model. Conclusions: Understanding the dynamics of CD8+ CXCR4/PSGL1 and NK CD56-KIR+ cells are essential for developing effective immunotherapy strategies and managing diseases where T-cell migration plays a significant role. Our findings highlight an exhausted TIME in CRPC compared to mHSPC after treatment. These results suggest that an altered TIME in CRPC may be associated with poorer prognosis, offering insights for future therapeutic approaches. T helper NK secreting chemokines (CD56-) T lymphocytes Memory CD4+ cells Natural Killer cells Cytotoxic NK cells (CD56 Dim) Memory CD8+ cells NK secreting chemokines and cytokines (CD56 bright) Cytotoxic CD8+ cells T regs Myeloid cells G-MDSC Dendritic cells CD11c-/CD14- M-MDSC CD11c+/CD14- Monocytes