PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

Abstract

Aims: Interaction between programmed death-1 ligand (PD-L1) and its receptor programmed death 1 (PD-1) on T cells inactivates antitumour immune responses. PD-L1 expression has been associated with poor prognosis in renal cell carcinoma (RCC) and predicts adverse outcome. This study was designed to evaluate the impact of PD-L1 expression and the immune microenvironment on the clinical outcome in Xp11 translocation renal cell carcinoma (TRCC) and, therefore, their potential relevance as prognostic biomarkers. Methods and results: The present retrospective analysis investigated expression of PD-L1 and immune cells CD8, CD4, CD3, forkhead box protein 3 (FoxP3) and PD-1 in TRCC compared to other types of RCC. FFPE specimens were collected between 2011 and 2017 from 311 patients who underwent nephrectomy at our institution for RCC. Specimens were immunostained for PD-L1, CD8, CD4, CD3, FoxP3 and PD-1, and an outcome analysis was conducted. PD-L1 expression rate was highest in TRCC (68%, 16 of 25), followed by mucinous tubular and spindle cell RCC and collecting duct carcinoma (33%, one of three), papillary RCC (27%, seven of 26), clear cell RCC (16%, 29 of 233), chromophobe RCC (11%, two of 18) and multilocular cystic RCC (0%, none of three). In TRCC, PD-L1 expression was associated with poor recurrence-free survival (RFS) (P = 0.041). The CD4 high and FoxP3 high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4 low and FOXP low groups. Conclusion: PD-L1 expression was higher in TRCC than in other types of RCC. High PD-L1 tumour cell expression and tumour infiltration by CD4 + and FoxP3 + immune cells were associated with poor RFS in TRCC.

The Clinical Significance of Routine Risk Categorization in Metastatic Renal Cell Carcinoma and its Impact on Treatment Decision-Making: A Systematic Review

“…Other challenges to the use of PD-L1 as a biomarker include the availability of numerous and treatment-specific antibodies, differential expression of PD-L1 between primary RCC and metastases, remodeling of PD-L1 expression by anti-angiogenic treatment, and the need to use refined Response Evaluation Criteria In Solid Tumors (RECIST) criteria to measure the atypical response to immune checkpoint inhibitors [32]. Nevertheless, PD-L1 may have potential as a prognostic biomarker in specific subtypes of RCC, such as Xp11 translocations, where high PD-L1 expression has been associated with lower recurrence-free survival [33].…”

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma

“…Prior studies have indicated that the prognostic and predictive value of T cells infiltrated in formalin-fixed and parrffin-embedded specimens in RCC (11,12). However, to the best of our knowledge, the present study is the first to identify the relationship between peripheral blood T lymphocyte subsets and the prognosis of patients with ccRCC.…”

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer

“…PD-L1 staining in tumor cells was significantly more frequent in papillary (18%) and chromophobe (19%), than in clear cell RCC (6%). Only few studies have earlier studied multiple RCC subtypes [ 18 , 24 , 26 , 28 , 49 , 50 ] and the existing data on differences in PD-L1 expression between RCC subtypes are conflicting. Our observations are in line with studies that have also reported lower rates of PD-L1 positivity in clear cell compared to papillary (0–16% vs 27–32% [ 18 , 26 ]) or in chromophobe RCC (0% vs 35% [ 18 ]).…”

“…Only few studies have earlier studied multiple RCC subtypes [ 18 , 24 , 26 , 28 , 49 , 50 ] and the existing data on differences in PD-L1 expression between RCC subtypes are conflicting. Our observations are in line with studies that have also reported lower rates of PD-L1 positivity in clear cell compared to papillary (0–16% vs 27–32% [ 18 , 26 ]) or in chromophobe RCC (0% vs 35% [ 18 ]). However, there are also studies showing equally high or even higher PD-L1 positivity rates in clear cell RCCs than in other renal tumor subtypes [ 26 , 28 , 49 ].…”