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

• Published in: Histopathology Vol. 76; no. 5; pp. 714 - 721
• Main Authors: Lee, Hyun J, Shin, Dong H, Lee, Yeon J, Lee, So J, Hwang, Chung S, Kim, Ahrong, Park, Won Y, Lee, Jung H, Choi, Kyung U, Kim, Jee Y, Lee, Chang H, Sol, Mee Y, Park, Sung W
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-04-2020
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; B7-H1 Antigen - biosynthesis; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - pathology; CD3 antigen; CD4; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Chromosomes, Human, X - genetics; Clear cell-type renal cell carcinoma; Collecting duct; Female; Forkhead protein; Forkhead Transcription Factors - immunology; FoxP3; Foxp3 protein; Humans; Infiltration; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - immunology; Kidney Neoplasms - pathology; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical prognosis; Metastases; Middle Aged; Nephrectomy; PD-1 protein; PD-L1 protein; PD‐L1; Prognosis; Renal cell carcinoma; Retrospective Studies; translocation renal cell carcinoma; Translocation, Genetic; Tumor Microenvironment - immunology; Tumors; tumour‐infiltrating lymphocytes; PD-L1; CD4; translocation renal cell carcinoma; FoxP3; tumour-infiltrating lymphocytes
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.14047

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 CD4high and FoxP3high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4low and FOXPlow 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.