Lactate Dehydrogenase-5 and Tumor-Infiltrating Lymphocytes in Prostate Cancer Patients Undergoing Radical...

Background/Objectives: Aerobic glycolysis is a standard mechanism that cancer cells use to support their anabolic processes. Lactate and proton production, byproducts of this LDHA-catalyzed transformation of pyruvate, may contribute to acidifying the tumor microenvironment and to repressing the cytotoxic activity of anti-tumor immune cells. Prostate cancer radiotherapy outcome could be diminished by cancer cell metabolism and immunosuppression. Methods: The tumor infiltrating lymphocyte (TIL) density was assessed in 110 prostate adenocarcinoma biopsies from patients treated with radical radiotherapy. Immunohistochemistry was performed to evaluate LDH5 expression by cancer cells (encoded by the LDHA gene). Results: Higher tumor stages (T3 and T4) were associated with lower TIL density (p = 0.02). Approximately half of the patients (51%) displayed strong LDH5 cancer cell expression, which was linked with advanced T-stage and higher Gleason scores (p = 0.05 and p = 0.01, respectively). High LDH5 expression was significantly correlated with low TIL density (p ≤ 0.0004). In univariate analysis, high LDH5 and low TIL density were associated with poor biochemical relapse-free survival (BRFS) (p ≤ 0.006). In multivariate analysis, TIL density, but not LDH5, was an independent predictor of BRFS (p = 0.03). Conclusions: LDH5 overexpression is associated with low tumor lymphocytic infiltration. Stratifying prostate carcinomas according to LDH5/TIL density identifies a group of patients with low TIL density and high LDH5 expression, who have a higher risk of tumor relapse. Targeting glycolysis to disrupt cancer cell metabolism offers an interesting research area for prostate cancer therapy.