ABSTRACT
Uterine cancer is the 4th most common cancer among women, with about 66,570 new cases in the United States every year. Late-stage uterine cancer patients have a less than 20% chance of survival due to limited effectiveness in treatment options. Immunotherapy is an emerging type of cancer treatment; however, it is only effective in a subtype of uterine cancer (∼20%). Major histocompatibility complex I (MHC-I) molecules have been researched as a main mechanism assisting cancerous cells to evade death by immune cell destruction. The goal of this project is to identify molecular regulators of MHC-I in uterine cancer to aid immunotherapy. Here, we analyzed the prognostic value of MHC-I molecules based on patient and molecular datasets from The Cancer Genome Atlas. MHC-I combined with T cell markers is associated with better prognosis in uterine cancer. Two molecular candidates, interferon regulatory factor 1 (IRF1) and proteasome subunit beta type-9 (PSMB9), were identified as potential MHC-I regulators. Wet-lab experiments confirmed the role of IRF1 in regulating MHC-I expression, though PSMB9 was found to be ineffective. Furthermore, uterine cancer expressed lower levels of IRF1 compared with normal uterine tissues. This finding brings significant insight into a potential immunotherapy target molecule for treating uterine cancer. Future development includes direct testing of T cell immune responses with IRF1 enhancements to prove its effectiveness on immune cell action.
- American Cancer Society, Key Statistics for Endometrial Cancer, https://www.cancer.org/cancer/endometrial-cancer/about/key-statistics.html.Google Scholar
- B.A. Dyer, C.H. Feng, R. Eskander, A.B. Sharabi, L.K. Mell, M. McHale, J.S. Mayadev, Current Status of Clinical Trials for Cervical and Uterine Cancer Using Immunotherapy Combined with Radiation, Int J Radiat Oncol Biol Phys, 109 (2021) 396-412.Google ScholarCross Ref
- U.P. Hegde, B. Mukherji, Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies, Cancer Immunol Immunother, 66 (2017) 1113-1121.Google ScholarCross Ref
- T. Okuda, A. Sekizawa, Y. Purwosunu, M. Nagatsuka, M. Morioka, M. Hayashi, T. Okai, Genetics of endometrial cancers, Obstet Gynecol Int, 2010 (2010) 984013.Google ScholarCross Ref
- K. Natarajan, H. Li, R.A. Mariuzza, D.H. Margulies, MHC class I molecules, structure and function, Rev Immunogenet, 1 (1999) 32-46.Google Scholar
- J. Bubenik, Tumour MHC class I downregulation and immunotherapy (Review), Oncol Rep, 10 (2003) 2005-2008.Google Scholar
- A.M. Cornel, I.L. Mimpen, S. Nierkens, MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy, Cancers (Basel), 12 (2020).Google Scholar
- Lin, G., Chai, J., Yuan, S., Mai, C., Cai, L., Murphy, R. W., Zhou, W., & Luo, J. (2016). VennPainter: A Tool for the Comparison and Identification of Candidate Genes Based on Venn Diagrams. PloS one, 11(4), e0154315.Google Scholar
- Jorgovanovic, D., Song, M., Wang, L. Roles of IFN-γ in tumor progression and regression: a review. Biomark Res 8, 49 (2020).Google ScholarCross Ref
- Xia, Y., Shen, S., & Verma, I. M. (2014). NF-κB, an active player in human cancers. Cancer immunology research, 2(9), 823–830.Google Scholar
- F. Dominguez, C. Simon, A. Quinonero, M.A. Ramirez, E. Gonzalez-Munoz, H. Burghardt, A. Cervero, S. Martinez, A. Pellicer, M. Palacin, F. Sanchez-Madrid, M. Yanez-Mo, Human endometrial CD98 is essential for blastocyst adhesion, PLoS One, 5 (2010) e13380.Google ScholarCross Ref
- P. Kralik, M. Ricchi, A Basic Guide to Real Time PCR in Microbial Diagnostics: Definitions, Parameters, and Everything, Front Microbiol, 8 (2017) 108.Google ScholarCross Ref
- H. Jiao, L. Zeng, S. Yang, J. Zhang, W. Lou, Knockdown EIF3C Suppresses Cell Proliferation and Increases Apoptosis in Pancreatic Cancer Cell, Dose Response, 18 (2020) 1559325820950061.Google ScholarCross Ref
- Q.F. Wu, C. Liu, M.H. Tai, D. Liu, L. Lei, R.T. Wang, M. Tian, Y. Lu, Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro, Acta Pharmacol Sin, 31 (2010) 361-366.Google ScholarCross Ref
- Wai Chung Chen, Tuo Hu, Chunbo He. The immune cell infiltration and landscape predicts clinical outcomes in gynecologic cancers [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl): Abstract nr PO067.Google Scholar
- S. Matikainen, T. Ronni, M. Hurme, R. Pine, I. Julkunen, Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells, Blood, 88 (1996) 114-123.Google ScholarCross Ref
Index Terms
- Restoring MHC-I Molecules to Potentiate Immunotherapy in Uterine Cancer
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