Soluble Programmed Death-Ligand 1 (sPD-L1) is Elevated in Aggressive Prostate Cancer Disease Among African Men

Abstract

Introduction: Programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men. Methods: Plasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined. Results: We found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014). Conclusions: Elevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy.

Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies

“…Higher sPD-L1 also correlated with the presence of metastasis in patients with renal cell carcinoma [72] and with the presence of liver metastasis in patients with NSCLC [73]. Elevated sPD-L1 also associated with the presence of muscle invasive disease and metastasis in patients with bladder cancer [21], lymph node metastasis in patients with colorectal cancer [54], higher Gleason scores in prostate cancer [59], less differentiated tumors and increased invasion and metastasis in renal cell carcinoma patients [58], and a greater residual tumor burden in patients with ovarian cancer [60]. Only a small number of reports (n = 4) have shown no association between sPD-L1 and tumor stage (in epithelial ovarian cancer [60], gastric cancer [74], hepatocellular carcinoma [51], and lung cancer [75]).…”

“…Most studies have found sPD-L1 to be elevated in cancer patients compared to healthy donors, with higher levels observed in patients with non-small cell lung cancer (NSCLC) [44][45][46][47], small cell lung cancer [48], gastric cancer [49,50], hepatocellular carcinoma [51][52][53], colorectal cancer [54], nasopharyngeal carcinoma [55], differentiated thyroid carcinoma [56], glioma [22], basal cell carcinoma [57], renal cell carcinoma [58], prostate cancer [59], and ovarian cancer [23,60,61]. However, some studies have reported no difference in the levels of sPD-L1 between healthy donors and patients with a variety of tumors including NSCLC [62], glioma [20], esophageal cancer [63], triple-negative breast cancer [64], and bladder cancer [21], and a few studies have described lower levels of sPD-L1 in patients with nasopharyngeal carcinoma [65], early breast cancer [66,67], gastric carcinoma [68], hepatocellular carcinoma [69], and clear cell renal cell carcinoma [70] compared to healthy donors.…”

“…Most studies have found sPD-1 to be elevated in cancer patients compared to healthy donors, with elevated levels reported in patients with NSCLC [47,104], esophageal cancer [63], differentiated thyroid carcinoma [56], hepatocellular carcinoma [105], nasopharyngeal carcinoma [55], basal cell carcinoma [57], triple-negative breast cancer [64], prostate cancer [59], and ovarian cancer [23]. One study reported no difference between the levels of sPD-1 in healthy donors and early breast cancer patients [67], while a few others reported lower levels of sPD-1 in patients with nasopharyngeal carcinoma [65], gastric cancer [106], and gastric carcinoma [68].…”

“…Higher levels of sPD-1 associate with a higher histological tumor grade/stage of cancer in patients with triple-negative breast cancer [64], ovarian cancer [23], and gastric cancer [106]. Similarly, higher sPD-1 correlated with increased tumor invasion in patients with renal cell carcinoma [58] and with a larger tumor size and the presence of cervical lymph node metastasis in patients with differentiated thyroid carcinoma [56]; however, sPD-1 did not correlate with Gleason scores in patients with prostate cancer [59]. Only one study in patients with nasopharyngeal carcinoma found that lower levels of sPD-1 associated with more advanced stages of disease [65].…”

The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

“…At present, PD-1/PD-L1 immunocheckpoint inhibitors have brought significant clinical benefits to some patients with PC. Further study will help guide the development of immunotherapy for advanced PC ( 122 , 123 ). Patients with high density of PD-1+ lymphocytes were at significantly higher risk of clinical failure, and it was positive association between a high density of PD-1+ lymphocytes and worse clinical failure-free survival ( 124 ).…”