Prostate cancer is the second most frequently diagnosed cancer in men worldwide, accounting for approximately 15% of all new cancer diagnoses in men (1). In 2020, the Global Cancer Observatory (Globocan) report indicated an annual worldwide incidence of 1.4 million prostate cancer cases, with approximately 375,304 deaths (2). Reports indicate that men of African ancestry suffer disproportionately from prostate cancer at a rate almost twice as high as men of European origin, irrespective of new treatment modalities (3–5).
The mainstay therapy for advanced prostate cancer remains androgen deprivation therapy (ADT)(6). Among patients with metastatic prostate cancer, various treatment options for metastatic castration-resistant prostate cancer (mCRPC) such as hormonal therapy, chemotherapy, and radiopharmaceuticals have shown significantly increased overall survival (OS). Still, these ultimately develop resistance (7, 8).
In the last decade, the introduction of immunotherapy which works through the augmentation of immune responses against cancers has yielded promising results and considerably changed the treatment landscape owing to its efficacy and minimal side effects (9, 10). Thus, immune checkpoint inhibitors have emerged as a complementary treatment arm in cancer clinical care and research (11, 12). The co-inhibitory receptor programmed death1 (PD-1) is expressed on activated T cells and B cells. Upon binding to its ligands PD-L1, which is expressed on macrophages, dendritic cells and some tumour cells, T cell activation is downregulated by inhibiting CD28 signaling (13). Besides being expressed on cell membranes, several extracellular (soluble) forms of PD-L1, including spliced variants and proteolytic cleavage forms, have been reported in various types of cancer(14). Soluble PD-L1 can bind to PD1 on T cells and suppress anti-tumour immunity, thus facilitating tumour growth. Blocking the PD1/PD-L1 interaction using immune checkpoint inhibitors have been shown to reduce tumour growth and increase overall survival of patients. (15).
Anti-PD1 antibody immunotherapy (e.g.nivolumab) and anti-PD-L1 antibody (e.g., atezolizumab) have demonstrated improved response rates and overall survival among patients with melanoma and renal cell carcinoma, respectively(16, 17).
The ongoing clinical trials show that immunotherapy might provide a promising approach for the future treatment of prostate cancer (18). Studies indicate that PD-L1 expression is up-regulated in prostate cancer tissues compared to paired benign prostate tissues. Similarly, high levels of PD-L1 expression have been shown to have a positive correlation with high Gleason scores and androgen receptor expression in patients with aggressive primary prostate cancer (19–21).
This study assessed the circulating levels of immune checkpoint molecules, PD-1 and PD-L1, among prostate cancer patients and normal healthy controls and their association with age, BMI, plasma PSA, and Gleason scores at the Uganda Cancer Institute.