Dana-Farber Cancer Institute, Boston, MA
Andre Poisl Fay , Marcella Callea , Kathryn P. Gray , Thai Huu Ho , Jiaxi Song , Ingrid Carvo , Megan E. Lampron , Laurence Albiges , Melissa L. Stanton , David F. McDermott , Michael B. Atkins , Gordon James Freeman , Michelle S. Hirsch , Sabina Signoretti , Toni K. Choueiri
Background: Programmed death-1 (PD-1) receptor negatively regulates T cell-mediated responses.PD-1 ligand (PD-L1) is aberrantly expressed in clear cell renal cell carcinoma (ccRCC) and is associated with worse prognosis. PD-L1 expression and its association with clinicopathological features/clinical outcome are unknown in non-ccRCC and benign kidney tumors (BKT). Methods: Formalin-fixed paraffin embedded (FFPE) specimens were obtained from 124 patients (pts) with chromophobe RCC (CHR), papillary RCC (PAP), translocation Xp11.2 RCC (TrL), collecting duct carcinoma (CDC), oncocytoma (ONC), and angiomyolipoma (AML). PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). The assay was validated using FFPE cell line controls known to be positive or negative for PD-L1 expression by flow cytometry. PD-L1 positivity (PD-L1+) was defined as ≥5% tumor cell membrane staining. For immune cells, a combined score based on the extent of infiltrate and percentage of positive cells was used. Baseline characteristics including stage/grade and outcome data [time to recurrence (TTR) and survival (OS)] were also collected. Results: Among 124 pts, 17 (13.7%) were considered PD-L1+ in tumor cells: 2/36 (5%) of CHR, 5/50 (10%) of PAP, 4/11 (36%) of TrL, 1/5 (20%) of CDC, 5/15 (33%) of ONC and 0/7 (0%) of AML. In non-ccRCC, PD-L1+ in tumor cells was significantly associated with higher stage (p=0.025) and grade (p=0.03), as well as lower OS on univariate analysis (p<0.001). On the other hand, PD-L1+ by immune cells was observed in 73 (58.8%) pts: 13/36 (36%) of CHR, 30/50 (60%) of PAP, 10/11 (91%) of TrL, 5/5 (100%) of CDC, 8/15 (53%) of ONC and 7/7 (100%) of AML. PD-L1+ in immune cells did not correlate with stage (p=0.3) or grade (p=0.1). In non-ccRCC, a trend for lower OS was observed in pts with PD-L1+ in immune cells (p=0.08). PD-L1+ in tumor cell membrane and immune cells were associated with lower TTR (p=0.009 and p=0.019, respectively) Conclusions: PD-L1 expression is variable in non-ccRCC and BKT and depends on histology. PD-L1+ on tumors cells, but not immune cells was associated with aggressive features. In non-ccRCC, PD-L1+ pts (by either tumor or immune cells) appear to present worse TTR and OS.
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