High IDO-1 expression in tumor endothelial cells is associated with response to immunotherapy in metastatic renal cell carcinoma.

Abstract

Nivolumab belongs to the standard therapy in the second-line setting of metastatic renal cell carcinoma (mRCC). Although deep and long-lasting responses are seen in some patients, the majority of patients will further progress. PD-L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO-1, a negative immune-regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO-1 and other immune inhibitory molecules (PD-L1, PD-L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin-fixed, paraffin-embedded sections of RCC specimens by immunohistochemistry. IDO-1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO-1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non-responders (33.3%, n = 3/9; P = .028), resulting in a better progression-free survival during immunotherapy (IDO-1 ≤ 10% vs >10%, median: 3.5 vs not estimated (NE) months, P = .01 by log-rank test). In addition, IDO-1 was positively correlated with CD8+ T cell expression (rs = .691, P = .006). PD-L1 expression on tumor cells was negative in 13 (86.7%) of 15 patients, irrespective of therapeutic response (responders vs non-responders: 83.3% vs 88.9%). No differences were noticed in the PD-L1 expression on tumor-infiltrating immune cells (PD-L1 < 1% in 66.7% of both responders and non-responders). In contrast to PD-L1, these results suggest that IDO-1 may be a more promising predictive biomarker for response to immune-based cancer therapy in mRCC.

• Authors: Andreas Seeber, Gerald Klinglmair, Josef Fritz, Fabian Steinkohl, Kai-Christian Zimmer, Friedrich Aigner, Wolfgang Horninger, Günther Gastl, Bettina Zelger, Andrea Brunner, Renate Pichler
• Journal: Cancer science (Cancer Sci) Vol. 109 Issue 5 Pg. 1583-1591 (May 2018) ISSN: 1349-7006 [Electronic] England
• PMID: 29498788 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• IDO1 protein, human
• Indoleamine-Pyrrole 2,3,-Dioxygenase

Topics

• Aged
• B7-H1 Antigen (analysis)
• Carcinoma, Renal Cell (enzymology, mortality, secondary, therapy)
• Endothelial Cells (enzymology)
• Female
• Humans
• Immunotherapy
• Indoleamine-Pyrrole 2,3,-Dioxygenase (physiology)
• Kidney Neoplasms (enzymology, mortality, pathology, therapy)
• Male
• Middle Aged