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Review
. 2020 Sep 18;12(9):2662.
doi: 10.3390/cancers12092662.

Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

Affiliations
Review

Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

Matthew D Tucker et al. Cancers (Basel). .

Abstract

Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most likely to benefit from immunotherapy and immunotherapy-based combinations have shown promise but have not yet affected clinical practice. PD-L1 expression via immunohistochemistry (IHC) has shown promise in a few clinical trials, although variations in the IHC assays as well as the use of different values for positivity presents unique challenges for this potential biomarker. Several other candidate biomarkers were investigated including tumor mutational burden, gene expression signatures, single gene mutations, human endogenous retroviruses, the gastrointestinal microbiome, and peripheral blood laboratory markers. While individually these biomarkers have yet to explain the heterogeneity of treatment response to immunotherapy, using aggregate information from these biomarkers may inform clinically useful predictive biomarkers.

Keywords: PD-L1; biomarkers; immunotherapy; renal cell carcinoma.

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Conflict of interest statement

Matthew D. Tucker reports no disclosures. Brian I. Rini reports: Research Funding to Institution: Pfizer, Merck, GNE/Roche, Aveo, Astra-Zeneca, BMS, Exelixis, Consulting: BMS, Pfizer, GNE/Roche, Aveo, Synthorx, Compugen, Merck, Corvus, Surface Oncology, 3DMedicines, Arravive, Alkermes, Arrowhead, GSK Stock: PTC therapeutics.

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Coppin C., Porzsolt F., Awa A., Kumpf J., Coldman A., Wilt T. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst. Rev. 2005:CD001425. doi: 10.1002/14651858.CD001425.pub2. - DOI - PubMed
    1. Klapper J.A., Downey S.G., Smith F.O., Yang J.C., Hughes M.S., Kammula U.S., Sherry R.M., Royal R.E., Steinberg S.M., Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: A retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008;113:293–301. doi: 10.1002/cncr.23552. - DOI - PMC - PubMed
    1. Mantia C.M., McDermott D.F. Vascular endothelial growth factor and programmed death-1 pathway inhibitors in renal cell carcinoma. Cancer. 2019;125:4148–4157. doi: 10.1002/cncr.32361. - DOI - PMC - PubMed
    1. Rini B.I., Battle D., Figlin R.A., George D.J., Hammers H., Hutson T., Jonasch E., Joseph R.W., McDermott D.F., Motzer R.J., et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC) J. Immunother. Cancer. 2019;7:354. doi: 10.1186/s40425-019-0813-8. - DOI - PMC - PubMed