Modern research beyond cytokine therapy has elucidated the various immune cells—including T cells, dendritic cells and natural killer (NK) cells—within renal cell tumors.16
In patients with RCC, there is the potential for a specific antitumor immune response and susceptibility to immune attack.23
The immune system modulates the activating and repressive signals that mediate surveillance of foreign antigens and a T-cell response to tumors.24
Tumor antigen-specific T cells have been isolated in peripheral blood of patients with RCC.25,26
Over the last several years, immunotherapy research has focused on inhibition of common targets within the tumor microenvironment.27
Researchers are also looking at additional activating and inhibiting signals that modulate T-cell responses. Further, investigators are exploring ways that tumor cells develop to avoid being recognized and killed by an immune response. This includes altering antigens, warding off natural killer (NK) cells through factors that suppress immunity, and alerting immune checkpoints that would otherwise recognize the tumor as a foreign body.16,28-30
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- Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115-124. doi: 10.1056/NEJMoa065044.
- Cairns P. Renal cell carcinoma. Cancer Biomarkers. 2011;9(1-6):461-473. doi: 10.3233/CBM-2011-0176.
- National Cancer Institute. Cancer stat facts: kidney and renal pelvis cancer. https://seer.cancer.gov/statfacts/html/kidrp.html. Accessed March 16, 2018.
- Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the Internal Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013;14(2):141-148. doi: 10.1016/S1470-2045(12)70559-4.
- Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16(3):293-300. doi: 10.1016/S1470-2045(14)71222-7.
- Rodriguez-Vida A, Hutson TE, Bellmunt J, et al. New treatment options for metastatic renal cell carcinoma. ESMO Open. 2017;2(2):e000185. doi:10.1136/esmoopen-2017-000185.
- . National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Kidney Cancer – NCCN Evidence Blocks. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney_blocks.pdf. Accessed April 3, 2018.
- . Escudier B, Bellmunt J, Negrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144-2150. doi: 10.1200/JCO.2009.26.7849.
- Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312-8. doi: 10.1200/JCO.2008.19.5511.
- Chowdhury S, Larkin JM, Gore ME. Recent advances in the treatment of renal cell carcinoma and the role of targeted therapies. Eur J Cancer. 2008;44(15):2152-2161. doi: 10.1016/j.ejca.2008.06.028.
- Mulders P. Vascular endothelial growth factor and mTOR pathways in renal cell carcinoma: differences and synergies of two targeted mechanisms. BJU Int. 2009;104(11):1585-1589. doi: doi: 10.1111/j.1464-410X.2009.08987.x.
- Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):668-696.
- Itsumi M, Tatsugami K. Immunotherapy for Renal Cell Carcinoma. Clin Dev Immunol. 2010. doi: 10.1155/2010/284581.
- Peggs KS, Quezada SA, Chambers CA, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies. J Exp Med. 2009;206(8):1717-1725. doi: 10.1084/jem.20082492.
- Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015-3029. doi: 10.1084/jem.20090847.
- Bedke J, Kruck S, Gakis G, et al. Checkpoint modulation – a new way to direct the immune system against renal cell carcinoma. Hum Vaccin Immunother. 2015;11(5):1201-1208. doi: doi: 10.1080/21645515.2015.1016657.
- Armstrong AC, Eaton D, Ewing JC. Cellular immunotherapy for cancer. BMJ. 2001;323:1289-1293. doi: 10.1136/bmj.323.7324.1289.
- O’Day SJ, Hamid O, Urba WJ. Targeting cytotoxic t-lymphocyte antigen-4 (CTLA-4). Cancer. 2007;110(12):2614-2627.
- Amos S, Duong C, Westwood J, et al. Autoimmunity associated with immunotherapy of cancer. Blood. 2011;118:499-509. doi: 10.1182/blood-2011-01-325266.
- Kitamura H, Honma I, Torigoe T, et al. Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma. J Urol. 2007;177:1269-1272.
- Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Frontiers in Pharmacology. 2017;8:561. doi: 10.3389/fphar.2017.00561.
- Ménétrier-Caux C, Bain C, Favrot MC, et al. Renal cell carcinoma induces interleukin 10 and prostaglandin E2 production by monocytes. Br J Cancer. 1999;79(1):119-130.
- Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. doi: 10.1038/nrc3239.
- Santarpia M, Karachaliou N. Tumor immune microenvironment characterization and response to anti-PD-1 therapy. Cancer Biol Med. 2015;12:74-78. doi: 10.7497/j.issn.2095-3941.2015.0022.
- Dörrschuck A, Schmidt A, Schnürer, et al. CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib–associated renal carcinoma antigens with ubiquitous or restricted tissue expression. Blood. 2004;104(8):2591-2599.
- Thompson RH, Gillett MD, Cheville JC, et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci USA. 2004;101(49):17174-17179.
- Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99(19):12293-12297.
- Markiewicz MA, Fallarino F, Ashikari A, Gajewski TF. Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A. Int Immunol. 2001;13(5):625-632.
- Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. Journal of Clinical Oncology. 2015;33(17):1974-1982. doi: 10.1200/JCO.2014.59.4358.
- Carlo MI, Voss MH, Motzer RJ. Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma. Nat Rev Urol. 2016;13(7):420-431. doi: 10.1038/nrurol.2016.103.
- Cho YH, Kim MS, Chung HS, Hwang EC. Novel immunotherapy in metastatic renal cell carcinoma. Investig Clin Urol. 2017;58(4):220-227. doi: 10.4111/icu.2017.58.4.220.
- King S, Pollack LA, Li J, et al. Continued increase in incidence of renal cell carcinoma, especially in young, patients and high grade disease: United States 2001 to 2010. J Urol. 2014:191(6):1665-1670. doi: 2013.12.046.
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