Exploring the prognostic implications of programmed death-ligand 1 expression in canine nodal lymphoma: Insights from surface membrane expression, transcript amount and plasmatic levels

: Programmed Death-Ligand 1 (PD-L1) is an immune-checkpoint molecule involved in tumor-induced immunotolerance. While few studies explored its role in canine B-cell lymphoma (BCL), comprehensive analysis across lymphoma immunophenotypes remains limited. This study investigated associations between time to progression (TTP) and lymphoma-specific survival (LSS) with PD-L1 expression, including surface membrane protein (mPD-L1), mRNA levels in nodal aspirates, and soluble protein (sPD-L1) plasmatic concentrations, in dogs with different nodal lymphoma immunophenotypes at initial presentation. Fifty-eight cases were evaluated: 38 BCL, 11 T-cell lymphomas not otherwise specified (T-NOS), and 9 T-zone lymphomas (TZL). No significant association was found between mPD-L1 expression, mRNA level, sPD-L1 concentration, and TTP or LSS. Although not significant, median TTP was longer in mPD-L1 negative cases in both BCL (306, 95%C.I. 130-482 vs. 136, 95%C.I. 102-170 days) and T-NOS (228, 95%C.I. 40-416 vs. 48, 95%C.I. 0-168 days). The same was true for LSS (273, 95%C.I. 58-386 vs. 191, 95%C.I. 23-236 days for BCL, and 282, 95%C.I. 60-504 vs. 121, 95%C.I. 77-165 days for T-NOS). Notably, the only two TZL cases that progressed were mPD-L1-positive. These findings suggest a potential prognostic role for mPD-L1, warranting further validation in larger cohorts in BCL and T-NOS nodal lymphomas. For TZL, extended follow-up studies are needed due to its indolent behavior. Although sPD-L1 and mRNA levels did not correlate with outcome, their diagnostic and prognostic utility merits further investigation and methodologic refinement.