Prognostic value of circulating CD11b + CD33 + myeloid cells in localized prostate cancer

Risk stratification in localized prostate cancer (PCa) relies on clinical and pathological parameters, as well as molecular assays that are often limited in accessibility. While circulating myeloid cells are associated with poor prognosis in advanced disease, their role in primary PCa remains unclear. This study aimed to determine whether circulating CD11b + CD33 + myeloid cells could serve as a minimally invasive, cost effective prognostic biomarker in localized PCa. We analyzed a prospective cohort of 79 patients with localized PCa undergoing radical prostatectomy. Circulating CD11b + CD33 + myeloid cells were quantified by flow cytometry. Associations between CD11b + CD33 + frequency and clinical parameters were evaluated, including EAU risk group, postoperative pathological features and biochemical recurrence (BCR). RNA sequencing was performed on FACS sorted circulating CD11b + CD33 + cells from 39 patients, including 15 from this prostatectomy cohort and 24 from an independent biopsy cohort. Circulating CD11b + CD33 + cell frequency was significantly higher in patients classified as high risk at diagnosis, versus intermediate (p = 0.0419) and low risk (p = 0.0087), and associated with adverse pathological features such as ISUP grade 4 and 5 (p = 0.0034) and perineural invasion (p = 0.0303). Transcriptomic profiling of these cells revealed distinct transcriptional programs in high risk versus intermediate risk patients, with enrichment of tumor promoting and immunosuppressive gene signatures. Higher circulating CD11b + CD33 + frequency associated with shorter BCR free survival (p = 0.028), particularly in high risk patients, after a median follow up of 31.8 months. Notably, the frequency of these cells outperformed the EAU risk classification, identifying a subset of high risk PCa patients at highest risk of early recurrence.To validate these findings, we analyzed the TCGA cohort of localized PCa patients (n = 329); although only tumor transcriptomic data were available, high intratumoral CD11b + CD33 + gene expression was associated with shorter disease free survival, especially in high risk patients. A custom four gene myeloid signature derived from genes upregulated in our cohort further refined risk stratification, predicting early relapse in high risk cases. Higher frequencies of circulating CD11b + CD33 + myeloid cells are observed in high risk localized PCa and associate with shorter BCR free survival. Remarkably, this myeloid expansion occurs even in organ confined disease, revealing an early systemic immune response previously unrecognized in localized PCa. Transcriptomic profiling confirmed enrichment of immunosuppressive and tumor promoting programs in these cells. Circulating CD11b + CD33 + frequency and associated gene signatures represent a novel prognostic biomarker, with potential to improve risk stratification in localized PCa, warranting validation in larger cohorts.