Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes.

In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients with testicular germ-cell tumors (GCTs). Expression of PD-L1 and VISTA was assessed by immunohistochemistry utilizing tissue microarrays. To estimate systemic inflammation neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were calculated. We found high PD-L1 and VISTA expression on tumor-associated immune cells (TAICs) in 89 (49.44%) and 63 (37.22%) of GCTs, respectively, whereas tumor cells besides trophoblastic elements were almost uniformly negative. High PD-L1 was associated with seminomatous histology and lower stage. Relapses in stage I patients occurred predominantly in cases with low numbers of PD-L1 and VISTA-expressing TAICs. In stage II/III disease, the combination of low VISTA-expressing TAICs and high PLR was identified as predictor of shorter event-free survival (HR 4.10; 1.48-11.36, = 0.006) and overall survival (HR 15.56, 95% CI 1.78-135.51, = 0.001) independently of tumor histology and location of metastases. We demonstrated that the assessment of immune checkpoint proteins on TAICs may serve as a valuable prognostic factor in patients with high-risk testicular GCTs. Further study is warranted to explore the predictive utility of these biomarkers in GCTs.