Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes
- PMID: 17132225
- PMCID: PMC1716012
- DOI: 10.1593/neo.06451
Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes
Abstract
Tumors can escape immune recognition and destruction through the induction of apoptosis in lymphocytes. Although renal cell carcinoma (RCC) is able to prevent immune recognition, only a few genes (such as FasL) that are relevant for RCC immune escape have been identified so far. We have previously shown that some apoptosis-inducing genes are overexpressed in RCC. We hypothesized that these genes could be part of the immune-escape strategy of these tumors. Here we report that CD70, a cytokine overexpressed in RCC, promotes lymphocyte apoptosis through interaction with its receptor CD27 and with the intracellular receptor-binding protein SIVA. Apoptosis increased after cocultivating lymphocytes with the RCC cell lines A498 and CAKI2. The addition of recombinant soluble CD70 to both native lymphocytes and a T-cell cell line resulted in increased lymphocyte apoptosis as well. Furthermore, induced apoptosis could be partially blocked with anti-CD27 and anti-CD70 antibodies. Our results strongly indicate a role for CD70 and CD27 receptor in lymphocyte apoptosis within the tumor environment. Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of RCC patients to develop an effective lymphocyte-mediated antitumor response.
Figures
Similar articles
-
pVHL/HIF-regulated CD70 expression is associated with infiltration of CD27+ lymphocytes and increased serum levels of soluble CD27 in clear cell renal cell carcinoma.Clin Cancer Res. 2015 Feb 15;21(4):889-98. doi: 10.1158/1078-0432.CCR-14-1425. Clin Cancer Res. 2015. PMID: 25691774
-
Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma.Cancer Res. 2002 May 1;62(9):2592-9. Cancer Res. 2002. PMID: 11980654
-
Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor.Cancer Res. 2001 Nov 1;61(21):7925-33. Cancer Res. 2001. PMID: 11691814
-
Control of lymphocyte function through CD27-CD70 interactions.Semin Immunol. 1998 Dec;10(6):491-9. doi: 10.1006/smim.1998.0154. Semin Immunol. 1998. PMID: 9826582 Review.
-
Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology.Immunol Rev. 2009 May;229(1):216-31. doi: 10.1111/j.1600-065X.2009.00774.x. Immunol Rev. 2009. PMID: 19426224 Review.
Cited by
-
CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.Cancer Discov. 2024 Jul 1;14(7):1176-1189. doi: 10.1158/2159-8290.CD-24-0102. Cancer Discov. 2024. PMID: 38583184 Free PMC article. Clinical Trial.
-
From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review.J Exp Clin Cancer Res. 2024 Feb 12;43(1):47. doi: 10.1186/s13046-024-02973-5. J Exp Clin Cancer Res. 2024. PMID: 38342925 Free PMC article. Review.
-
Soluble CD27 as a predictive biomarker for intra-tumoral CD70/CD27 interaction in nasopharyngeal carcinoma.Cancer Sci. 2024 Apr;115(4):1073-1084. doi: 10.1111/cas.16079. Epub 2024 Jan 27. Cancer Sci. 2024. PMID: 38279834 Free PMC article.
-
Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma.iScience. 2023 Oct 31;26(12):108367. doi: 10.1016/j.isci.2023.108367. eCollection 2023 Dec 15. iScience. 2023. PMID: 38025776 Free PMC article.
-
Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma.Hum Vaccin Immunother. 2023 Dec 15;19(3):2276629. doi: 10.1080/21645515.2023.2276629. Epub 2023 Nov 10. Hum Vaccin Immunother. 2023. PMID: 37947202 Free PMC article. Review.
References
-
- Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol Today. 1999;20:158–160. - PubMed
-
- Uzzo RG, Rayman P, Rolenko V, Clark PE, Bloom T, Ward AM, Molto L, Tannenbaum C, Worford LJ, Bukowski R, et al. Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res. 1999;5:1219–1229. - PubMed
-
- Diegmann J, Junker K, Gerstmayer B, Bosio A, Hindermann W, Rosenhahn J, von Eggeling F. Identification of CD70 as a diagnostic biomarker for clear cell renal cell carcinoma by gene expression profiling, real-time RT-PCR and immunohistochemistry. Eur J Cancer. 2005;41:1794–1801. - PubMed
-
- Junker K, Hindermann W, von Eggeling F, Diegmann J, Haessler K, Schubert J. CD70: a new tumor specific biomarker for renal cell carcinoma. J Urol. 2005;173:2150–2153. - PubMed
-
- Diegmann J, Tomiuk S, Sanjmyatav J, Junker K, Hindermann W, von Eggeling Comparative transcriptional and functional profiling of clear cell and papillary renal cell carcinoma. Int J Mol Med. 2006;18:395–403. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials