Tumor Suppressor Gene P29ing4 is Overexpressed and Induces a CD8 T Effector Cell Response in Human Renal Cell Carcinoma
Nichiporuk Stumpf E1, Yeung M2, Grimm MR3, Grimmig T1, Stern PL4, Moench R1, Lebedeva T5, Pal S6, Tripathi S2, Bonventre JV2, Chandraker A2, Heemann U7, Tsaur I8, Blaheta R8, Lissner R1, Germer CT9, Riedmiller H10, Gasser M9*# and Waaga-Gasser AM1,2*#
- *Corresponding Authors:
- Waaga-Gasser AM
Department of Surgery I, Molecular Oncology and Immunology
University of Wuerzburg, Germany
E-mail: [email protected] / [email protected]
- Gasser M
Department of Surgery I
University of Wuerzburg, Wuerzburg, Germany
Received date: May 29, 2017; Accepted date: June 26, 2017; Published date: June 30, 2017
Citation: Stumpf EN, Yeung M, Grimm MR, Grimmig T, Stern PL, et al. (2017) Tumor Suppressor Gene P29ing4 is Overexpressed and Induces a CD8 T Effector Cell Response in Human Renal Cell Carcinoma. J Clin Cell Immunol 8:511. doi: 10.4172/2155-9899.1000511
Copyright: © 2017 Stumpf EN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: ING1 and ING4 are identified as candidate tumor suppressor genes acting in regulation of DNA damage responses and apoptosis through modulation of p53. Their defective function promotes tumor growth in melanoma and breast cancer. Our aim was to determine the overexpression of relevant p33ING1b and p29ING4 isoforms in patients with Renal Cell Cancer (RCC).
Methods: Peripheral Blood Mononuclear Cells (PBMCs) from tumor patients (Robson stage I-IV) were stimulated with overlapping peptides of p33ING1b/p29ING4 and results were compared with expression profiles in primary tumors.
Results: Early-stage and late-stage tumors demonstrated upregulated ING-isoform gene and protein expression. Early cancers were characterized by increased CD8 and IFN-γ protein and gene expression. Significant p33ING1b and p29ING4 tumor-specific CD8 T effector cell responses from PBMCs of the analyzed tumor patients were observed. Interestingly, peptide sequences p33ING1b (aa259-268) and p29ING4 (aa149-158) elicited significant IFN-γ responses indicative for anti-tumor immune responses while IL-2 responses were detected only for p29ING4 (aa149-158), suggesting inducible T effector cell responses.
Conclusion: T effector cell analysis against p29ING4 (aa149-158) suggests a promising candidate for in vivo induction of tumor-reactive CD8 T effector cells in patients with renal cell cancer.