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

Area of Science:

• Oncology
• Cancer Metabolism
• Immunotherapy

Background:

• Aerobic glycolysis supports cancer cell growth and may create an immunosuppressive tumor microenvironment.
• Lactate and proton production from glycolysis can lower tumor pH, hindering anti-tumor immune cell function.
• Prostate cancer radiotherapy effectiveness may be compromised by cancer metabolism and immune suppression.

Purpose of the Study:

• To investigate the association between lactate dehydrogenase 5 (LDH5) expression, tumor-infiltrating lymphocyte (TIL) density, and radiotherapy outcomes in prostate cancer.
• To explore the role of cancer cell metabolism and immune infiltration in prostate cancer progression and treatment response.

Main Methods:

• Assessed TIL density in 110 prostate adenocarcinoma biopsies from patients treated with radical radiotherapy.
• Utilized immunohistochemistry to evaluate LDH5 expression in cancer cells (LDHA gene).
• Correlated LDH5 expression and TIL density with tumor stage, Gleason score, and biochemical relapse-free survival (BRFS).

Main Results:

• Higher tumor stages (T3-T4) correlated with lower TIL density (p=0.02).
• 51% of patients showed strong LDH5 expression, linked to advanced T-stage and higher Gleason scores (p=0.05, p=0.01).
• High LDH5 expression significantly correlated with low TIL density (p≤0.0004) and was associated with poor BRFS in univariate analysis (p≤0.006).
• TIL density, not LDH5, independently predicted BRFS in multivariate analysis (p=0.03).

Conclusions:

• LDH5 overexpression is linked to reduced tumor lymphocytic infiltration in prostate cancer.
• Patients with high LDH5 and low TIL density face a higher risk of tumor relapse after radiotherapy.
• Targeting cancer cell glycolysis presents a promising therapeutic strategy for prostate cancer.