Home LiteratureArticle Details
PMID: 21917625 Published · ppublish English Historical Article Journal Article Review

Role of immunotherapy for renal cell cancer in 2011.

Journal of the National Comprehensive Cancer Network : JNCCN ·Vol. 9 ·No. 9 ·2011-09-01 ·Pages 1011-8

George S, Pili R, Carducci MA, Kim JJ

Abstract

High-dose interleukin-2 (IL-2) and interferon were the most commonly administered therapies before the recent introduction of targeted agents, including vascular endothelial growth factor and mammalian target of rapamycin pathway inhibitors. Although the new agents result in a progression-free survival benefit, high-dose IL-2 remains the only agent with proven efficacy in producing durable complete and partial responses in patients with metastatic renal cell carcinoma (RCC). Furthermore, although the use of single-agent interferon has decreased significantly since the introduction of targeted therapy, it remains in the frontline setting in combination with bevacizumab as a result of 2 large phase III trials. Lastly, improved understanding of immune regulation has led to the advancement of targeted immunotherapy using immune checkpoint inhibitors that have shown promising activity and are moving forward in clinical development. This article focuses on the current status of immunotherapy in the management of metastatic RCC.

MeSH Terms
Animals Carcinoma, Renal Cell/mortality,pathology,therapy History, 21st Century Humans Immunotherapy/adverse effects,history Treatment Outcome
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
George Saby
Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Saby.George@RoswellPark.org
Pili Roberto
Carducci Michael A
Kim Jenny J
References (63)
63 references, click to expand
  1. Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma.
    Cancer Res. 2003 Aug 1;63(15):4481-9 PMID: 12907621
  2. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy.
    J Clin Oncol. 1995 Mar;13(3):688-96 PMID: 7884429
  3. Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma.
    Clin Cancer Res. 2007 Mar 15;13(6):1749-56 PMID: 17363528
  4. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
    Science. 1995 Nov 10;270(5238):985-8 PMID: 7481803
  5. Allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of metastatic renal cell carcinoma -- single center experience.
    Neoplasma. 2005;52(3):238-42 PMID: 15875086
  6. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients.
    Clin Cancer Res. 2009 Mar 15;15(6):2148-57 PMID: 19276286
  7. Sarcomatoid renal cell carcinoma: biologic behavior, prognosis, and response to combined surgical resection and immunotherapy.
    J Clin Oncol. 1999 Feb;17(2):523-8 PMID: 10080595
  8. Using histone deacetylase inhibitors to enhance Foxp3(+) regulatory T-cell function and induce allograft tolerance.
    Immunol Cell Biol. 2009 Mar-Apr;87(3):195-202 PMID: 19172156
  9. Cancer statistics, 2010.
    CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300 PMID: 20610543
  10. Guidelines for the safe administration of high-dose interleukin-2.
    J Immunother. 2001 Jul-Aug;24(4):287-93 PMID: 11565830
  11. B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival.
    Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10391-10396 PMID: 16798883
  12. Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience.
    Bone Marrow Transplant. 2005 Feb;35(3):253-60 PMID: 15543195
  13. Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up.
    J Clin Oncol. 1993 Jul;11(7):1368-75 PMID: 8315435
  14. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
    J Clin Oncol. 2010 Jul 1;28(19):3167-75 PMID: 20516446
  15. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.
    Science. 2001 Jan 12;291(5502):319-22 PMID: 11209085
  16. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2.
    JAMA. 1994 Mar 23-30;271(12):907-13 PMID: 8120958
  17. Sunitinib efficacy against advanced renal cell carcinoma.
    J Urol. 2007 Nov;178(5):1883-7 PMID: 17868732
  18. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
    Eur J Cancer. 2009 Jan;45(2):228-47 PMID: 19097774
  19. Synergistic in vivo antitumor effect of the histone deacetylase inhibitor MS-275 in combination with interleukin 2 in a murine model of renal cell carcinoma.
    Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4538-46 PMID: 17671140
  20. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
    Immunity. 1995 Nov;3(5):541-7 PMID: 7584144
  21. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
    J Clin Oncol. 2010 Feb 20;28(6):1061-8 PMID: 20100962
  22. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial.
    Lancet. 2007 Dec 22;370(9605):2103-11 PMID: 18156031
  23. MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma.
    Clin Cancer Res. 2003 Mar;9(3):947-54 PMID: 12631591
  24. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
    J Clin Oncol. 2006 May 20;24(15):2283-9 PMID: 16710025
  25. Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: toxicity, clinical response, and immunological response to minor histocompatibility antigens.
    Clin Cancer Res. 2004 Dec 1;10(23):7799-811 PMID: 15585611
  26. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma.
    Clin Cancer Res. 2007 Mar 15;13(6):1757-61 PMID: 17363529
  27. Improved survival with ipilimumab in patients with metastatic melanoma.
    N Engl J Med. 2010 Aug 19;363(8):711-23 PMID: 20525992
  28. Deacetylase inhibition promotes the generation and function of regulatory T cells.
    Nat Med. 2007 Nov;13(11):1299-307 PMID: 17922010
  29. PD-1 and its ligands in tolerance and immunity.
    Annu Rev Immunol. 2008;26:677-704 PMID: 18173375
  30. Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe.
    Ann Oncol. 2006 Jul;17(7):1134-40 PMID: 16648196
  31. Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells.
    Cancer Res. 2003 May 1;63(9):2127-33 PMID: 12727829
  32. 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 U S A. 2002 Sep 17;99(19):12293-7 PMID: 12218188
  33. Long-term follow-up of metastatic renal cancer patients undergoing reduced-intensity allografting.
    Bone Marrow Transplant. 2009 Aug;44(4):237-42 PMID: 19234510
  34. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer.
    J Clin Oncol. 1999 Sep;17(9):2859-67 PMID: 10561363
  35. Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy.
    J Immunother. 2005 Sep-Oct;28(5):488-95 PMID: 16113605
  36. CTLA-4 can function as a negative regulator of T cell activation.
    Immunity. 1994 Aug;1(5):405-13 PMID: 7882171
  37. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients.
    Clin Cancer Res. 2008 Oct 15;14(20):6674-82 PMID: 18927310
  38. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
    Immunity. 1999 Aug;11(2):141-51 PMID: 10485649
  39. Immunotherapy of metastatic renal cell carcinoma.
    Cancer. 2009 May 15;115(10 Suppl):2298-305 PMID: 19402060
  40. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
    N Engl J Med. 2007 Jan 11;356(2):115-24 PMID: 17215529
  41. Inhaled interleukin-2 therapy in pulmonary metastatic renal cell carcinoma: six years of experience.
    Cancer J Sci Am. 1997 Dec;3 Suppl 1:S98-105 PMID: 9457403
  42. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis.
    J Immunother. 2007 Nov-Dec;30(8):825-30 PMID: 18049334
  43. Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma.
    Clin Cancer Res. 2011 Apr 1;17(7):1915-23 PMID: 21355078
  44. Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma.
    Cancer. 2011 Feb 15;117(4):758-67 PMID: 20922784
  45. Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials.
    Cancer. 2003 Dec 15;98(12):2566-75 PMID: 14669275
  46. Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) alone or administered in combination with interferon-alpha (IFN-alpha): a phase 2 trial.
    J Immunother. 2009 Sep;32(7):765-72 PMID: 19561532
  47. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators.
    Lancet. 1999 Jan 2;353(9146):14-7 PMID: 10023944
  48. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206.
    J Clin Oncol. 2008 Nov 20;26(33):5422-8 PMID: 18936475
  49. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3360-5 PMID: 17360651
  50. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.
    J Natl Cancer Inst. 2000 Feb 2;92(3):205-16 PMID: 10655437
  51. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial.
    Lancet. 2008 Aug 9;372(9637):449-56 PMID: 18653228
  52. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma.
    Cancer. 2010 Apr 1;116(7):1757-66 PMID: 20143437
  53. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes.
    Cancer Res. 2009 Feb 15;69(4):1553-60 PMID: 19201693
  54. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma.
    J Clin Oncol. 2006 Jan 1;24(1):16-24 PMID: 16330672
  55. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.
    N Engl J Med. 2007 May 31;356(22):2271-81 PMID: 17538086
  56. Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
    J Clin Oncol. 2009 Sep 1;27(25):4068-75 PMID: 19652072
  57. Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma.
    J Exp Med. 2002 Sep 2;196(5):619-28 PMID: 12208877
  58. Sorafenib in advanced clear-cell renal-cell carcinoma.
    N Engl J Med. 2007 Jan 11;356(2):125-34 PMID: 17215530
  59. Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients.
    Clin Cancer Res. 2009 Aug 1;15(15):4986-92 PMID: 19622576
  60. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement.
    Immunity. 1996 Jun;4(6):535-43 PMID: 8673700
  61. Treatment selection for patients with metastatic renal cell carcinoma: identification of features favoring upfront IL-2-based immunotherapy.
    Med Oncol. 2009;26 Suppl 1:18-22 PMID: 19165638
  62. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.
    J Clin Oncol. 2002 Jan 1;20(1):289-96 PMID: 11773181
  63. Kidney cancer: the Cytokine Working Group experience (1986-2001): part II. Management of IL-2 toxicity and studies with other cytokines.
    Med Oncol. 2001;18(3):209-19 PMID: 11917945
Article Info
Journal
Journal of the National Comprehensive Cancer Network : JNCCN
Abbr.
J Natl Compr Canc Netw
ISSN
1540-1413
DOI
10.6004/jnccn.2011.0085
Email
saby.george@roswellpark.org
Published
2011-09-01
Pages
1011-8
Language
English
Region
United States
NLM ID
101162515
PMCID
PMC4020430
Subset
IM
Grants
NCI NIH HHS · P30 CA006973 · United States
Databases
ClinicalTrials.gov
NCT00441337, NCT01354431
External Links
PubMed source DOI: 10.6004/jnccn.2011.0085 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2