Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

Main Article Content

Hidenori Kawashima
Yasunori Kimura

Keywords

Renal cell carcinoma, immunotherapy, cytokine, peptide-based vaccine, tumor antigen, immune checkpoint inhibitor

Abstract

Metastatic lesions of renal cell carcinoma (RCC) occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets.

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References

1. Umeda T, Niijima T. Phase II study of alpha interferon on renal cell carcinoma. Summary of three collaborative trials. Cancer. 1986;58(6):1231-5.
Doi: http://dx.doi.org/10.1002/1097-0142(19860915)58:6<1231::AID-CNCR2820580610>3.0.CO;2-#

2. Esa A et al. Hinyokika Kiyo 2010; 56: 134. (In Japanese).

3. Kawashima H. The present state and the future perspective of immunotherapy of renal cell carcinoma. Nihon Rinsho 2015; 73:167–174. (In Japanese). [PMid:25626324].

4. Childs R et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343(11):750-8.
Doi: http://dx.doi.org/10.1056/NEJM200009143431101

5. Aoyama Y et al. Reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma. Int J Urol. 2003;10(11):610-4; discussion 615.
Doi: http://dx.doi.org/10.1046/j.1442-2042.2003.00700.x

6. Latif F et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260(5112):1317-20. Doi: http://dx.doi.org/10.1126/science.8493574

7. Shuin T et al. Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res. 1994 Jun 1;54(11):2852-5. [PMid:8187067]

8. Naito S et al. Prognosis of Japanese metastatic renal cell carcinoma patients in the cytokine era: a cooperative group report of 1463 patients. Eur Urol. 2010;57(2):317-25.
Doi: http://dx.doi.org/10.1016/j.eururo.2008.12.026

9. Akaza H et al. Successful outcomes using combination therapy of interleukin-2 and interferon-alpha for renal cell carcinoma patients with lung metastasis. Jpn J Clin Oncol. 2010;40(7):684-9. Doi: http://dx.doi.org/10.1093/jjco/hyq027

10. Bukowski RM. Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer. 1997;80(7):1198-220.
Doi: http://dx.doi.org/10.1002/(SICI)1097-0142(19971001)80:7<1198::AID-CNCR3>3.0.CO;2-H

11. Uemura H, Fujimoto K, Tanaka M, Yoshikawa M, Hirao Y, Uejima S, Yoshikawa K, Itoh K. A phase I trial of vaccination of CA9 derived peptides for HLA A24 positive patients with cytokine refractory metastatic renal cell carcinoma. Clin Cancer Res. 2006;12(6):1768-75. Doi: http://dx.doi.org/10.1158/1078-0432.CCR-05-2253

12. Iiyama T et al. WT1 (Wilms' tumor 1) peptide immunotherapy for renal cell carcinoma. Microbiol Immunol. 2007;51(5):519-30. Doi: http://dx.doi.org/10.1111/j.1348-0421.2007.tb03940.x

13. Sato E et al. Identification of an immunogenic CTL epitope of HIFPH3 for immunotherapy of renal cell carcinoma. Clin Cancer Res. 2008;14(21):6916-23.
Doi: http://dx.doi.org/10.1158/1078-0432.CCR-08-0466

14. Walter S et al. Multipeptide immune response to cancer vaccine IMA901 after single dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18(8):1254-61.
Doi: http://dx.doi.org/10.1038/nm.2883

15. Yoshimura K, Minami T, Nozawa M, Uemura H. Phase I clinical trial of human vascular endothelial growth factor receptor 1 peptide vaccines for patients with metastatic renal cell carcinoma. Br J Cancer. 2013;108(6):1260-6. Doi: http://dx.doi.org/10.1038/bjc.2013.90

16. Pavone L, Fanti G, Bongiovanni C, Goldoni M, Alberici F, Bonomini S, Cristinelli L, Buzio C. Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-alpha in patients with renal cell carcinoma. Med Oncol. 2009;26(1):38-44. Doi: http://dx.doi.org/10.1007/s12032-008-9078-7

17. Wang G, Tschoi M, Spolski R, Lou Y, Ozaki K, Feng C, Kim G, Leonard WJ, Hwu P. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res. 2003;63(24):9016-22. [PMid:14695220].

18. Polimeno M et al. Regulatory T cells, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma. BJU Int. 2013;112(5):686-96. Doi: http://dx.doi.org/10.1111/bju.12068

19. Taniguchi M, Seino K, Nakayama T. The NKT cell system: bridging innate and acquired immunity. Nat Immunol. 2003;4(12):1164-5. Doi: http://dx.doi.org/10.1038/ni1203-1164

20. Motohashi S, Okamoto Y, Yoshino I, Nakayama T. Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer. Clin Immunol. 2011;140(2):167-76. Doi: http://dx.doi.org/10.1016/j.clim.2011.01.009

21. Kawashima H, Obayashi A, Kawamura M, Masaki S, Tamada S, Iguchi T, Uchida J, Kuratsukuri K, Tanaka T, Nakatani T. Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumor antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides. BJU Int. 2014;113(2):320-32.
Doi: http://dx.doi.org/10.1111/bju.12499

22. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245-52. Doi: http://dx.doi.org/10.1038/ni1271

23. Sehrawat S, Reddy PB, Rajasagi N, Suryawanshi A, Hirashima M, Rouse BT. Galectin-9/TIM-3 interaction regulates virus-specific primary and memory CD8 T cell response. PLoS Pathog. 2010;6(5):e1000882. Doi: http://dx.doi.org/10.1371/journal.ppat.1000882

24. Ngiow SF, Teng MW, Smyth MJ. Prospects for TIM3-targeted antitumor immunotherapy. Cancer Res. 2011;71(21):6567-71. Doi: http://dx.doi.org/10.1158/0008-5472.CAN-11-1487

25. Lee CS, Cragg M, Glennie M, Johnson P. Novel antibodies targeting immune regulatory checkpoints for cancer therapy. Br J Clin Pharmacol. 2013;76(2):233-47.
Doi: http://dx.doi.org/10.1111/bcp.12164

26. Chen K, Tu Y, Zhang Y, Blair HC, Zhang L, Wu C. PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J Biol Chem. 2008;283(5):2508-17.
Doi: http://dx.doi.org/10.1074/jbc.M707307200

27. Li Y, Dai C, Wu C, Liu Y. PINCH 1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. J Am Soc Nephrol. 2007;18(9):2534-43.
Doi: http://dx.doi.org/10.1681/ASN.2007030315

28. Kawashima H, Masaki S, Kawamura M. Induction of HLA-A*33-restricted cytotoxic lymphocytes against renal cell carcinoma targeting galectin 9 and PINCH. Biomed Rep. 2014;2(6):809-812.
Doi: http://dx.doi.org/10.3892/br.2014.334

29. Topalian SL et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-54. Doi: http://dx.doi.org/10.1056/NEJMoa1200690

30. Mullard A. New checkpoint inhibitors ride the immunotherapy tsunami. Nat Rev Drug Discov. 2013;12(7):489-92. Doi: http://dx.doi.org/10.1038/nrd4066

31. Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ. Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Res. 2011;71(10):3540-51. Doi: http://dx.doi.org/10.1158/0008-5472.CAN-11-0096