Increased circulating polymorphonuclear myeloid-derived suppressor cells are associated with prognosis of metastatic castration-resistant prostate cancer

• Published in: Frontiers in immunology Vol. 15; p. 1372771
• Main Authors: Kobayashi, Takuro, Nagata, Masayoshi, Hachiya, Tsuyoshi, Wakita, Haruhiko, Ikehata, Yoshihiro, Takahashi, Keiji, China, Toshiyuki, Shimizu, Fumitaka, Lu, Jun, Jin, Yiming, Lu, Yan, Ide, Hisamitsu, Horie, Shigeo
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 03.06.2024
• Subjects: castration-resistant prostate cancer; hormone-sensitive prostate cancer; Immunology; myeloid-derived suppressor cell; prognosis; tumor microenvironment
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1372771

Introduction Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators. Methods We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival. Results The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10 −5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m 2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05–11.56, P = 0.042). Discussion PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.