Post-Translational Modifications in Tumor-Associated Antigens As a Platform for Novel Immuno-Oncology Therapies

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Jan 8

PMID 36612133

Authors

Anurag Kumar Srivastava

Giorgia Guadagnin

Paola Cappello

Francesco Novelli

Affiliations

Soon will be listed here.

Abstract

Post-translational modifications (PTMs) are generated by adding small chemical groups to amino acid residues after the translation of proteins. Many PTMs have been reported to correlate with tumor progression, growth, and survival by modifying the normal functions of the protein in tumor cells. PTMs can also elicit humoral and cellular immune responses, making them attractive targets for cancer immunotherapy. This review will discuss how the acetylation, citrullination, and phosphorylation of proteins expressed by tumor cells render the corresponding tumor-associated antigen more antigenic and affect the immune response in multiple cancers. In addition, the role of glycosylated protein mucins in anti-cancer immunotherapy will be considered. Mucin peptides in combination with stimulating adjuvants have, in fact, been utilized to produce anti-tumor antibodies and vaccines. Finally, we will also outline the results of the clinical trial exploiting glycosylated-MUC1 as a vaccine in different cancers. Overall, PTMs in TAAs could be considered in future therapies to result in lasting anti-tumor responses.

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References

MacLean G, Reddish M, Koganty R, Longenecker B . Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol. 1996; 19(1):59-68. DOI: 10.1097/00002371-199601000-00007. View

Hanski C, Hofmeier M, Schmitt-Graff A, Riede E, Hanski M, Borchard F . Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary. J Pathol. 1997; 182(4):385-91. DOI: 10.1002/(SICI)1096-9896(199708)182:4<385::AID-PATH861>3.0.CO;2-Q. View

Yu J, Hubbard-Lucey V, Tang J . The global pipeline of cell therapies for cancer. Nat Rev Drug Discov. 2019; 18(11):821-822. DOI: 10.1038/d41573-019-00090-z. View

Butts C, Socinski M, Mitchell P, Thatcher N, Havel L, Krzakowski M . Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2013; 15(1):59-68. DOI: 10.1016/S1470-2045(13)70510-2. View

Yuzhalin A . Citrullination in Cancer. Cancer Res. 2019; 79(7):1274-1284. DOI: 10.1158/0008-5472.CAN-18-2797. View

Choudhary C, Weinert B, Nishida Y, Verdin E, Mann M . The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol. 2014; 15(8):536-50. DOI: 10.1038/nrm3841. View

Ramazi S, Zahiri J . Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford). 2021; 2021. PMC: 8040245. DOI: 10.1093/database/baab012. View

Li Y, Depontieu F, Sidney J, Salay T, Engelhard V, Hunt D . Structural basis for the presentation of tumor-associated MHC class II-restricted phosphopeptides to CD4+ T cells. J Mol Biol. 2010; 399(4):596-603. PMC: 2904831. DOI: 10.1016/j.jmb.2010.04.037. View

Mohebtash M, Tsang K, Madan R, Huen N, Poole D, Jochems C . A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer. Clin Cancer Res. 2011; 17(22):7164-73. PMC: 3227395. DOI: 10.1158/1078-0432.CCR-11-0649. View

10.

Apostolopoulos V, Pietersz G, Tsibanis A, Tsikkinis A, Drakaki H, Loveland B . Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Res. 2006; 8(3):R27. PMC: 1557739. DOI: 10.1186/bcr1505. View

11.

Liu Y, Zhao Q, Xu F, Wang K, Zhao Y, Chen H . Dysregulation of phosphoproteins in hepatocellular carcinoma revealed via quantitative analysis of the phosphoproteome. Oncol Lett. 2021; 21(2):117. PMC: 7779902. DOI: 10.3892/ol.2020.12378. View

12.

Miles D, Roche H, Martin M, Perren T, Cameron D, Glaspy J . Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist. 2011; 16(8):1092-100. PMC: 3228158. DOI: 10.1634/theoncologist.2010-0307. View

13.

Zhao D, Zou S, Liu Y, Zhou X, Mo Y, Wang P . Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell. 2013; 23(4):464-76. PMC: 3885615. DOI: 10.1016/j.ccr.2013.02.005. View

14.

Rakha E, Boyce R, Abd El-Rehim D, Kurien T, Green A, Paish E . Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol. 2005; 18(10):1295-304. DOI: 10.1038/modpathol.3800445. View

15.

Lim J, Wollaston-Hayden E, Teo C, Hausman D, Wells L . Quantitative secretome and glycome of primary human adipocytes during insulin resistance. Clin Proteomics. 2014; 11(1):20. PMC: 4055909. DOI: 10.1186/1559-0275-11-20. View

16.

Petersen J, Wurzbacher S, Williamson N, Ramarathinam S, Reid H, Nair A . Phosphorylated self-peptides alter human leukocyte antigen class I-restricted antigen presentation and generate tumor-specific epitopes. Proc Natl Acad Sci U S A. 2009; 106(8):2776-81. PMC: 2650342. DOI: 10.1073/pnas.0812901106. View

17.

Garcia-Labastida L, Garza-Guajardo R, Barboza-Quintana O, Rodriguez-Sanchez I, Ancer-Rodriguez J, Flores-Gutierrez J . CDX-2, MUC-2 and B-catenin as intestinal markers in pure mucinous carcinoma of the breast. Biol Res. 2014; 47:43. PMC: 4177067. DOI: 10.1186/0717-6287-47-43. View

18.

Eichler J . Protein glycosylation. Curr Biol. 2019; 29(7):R229-R231. DOI: 10.1016/j.cub.2019.01.003. View

19.

Kumai T, Ishibashi K, Oikawa K, Matsuda Y, Aoki N, Kimura S . Induction of tumor-reactive T helper responses by a posttranslational modified epitope from tumor protein p53. Cancer Immunol Immunother. 2014; 63(5):469-78. PMC: 11028558. DOI: 10.1007/s00262-014-1533-z. View

20.

Soares M, Mehta V, Finn O . Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. J Immunol. 2001; 166(11):6555-63. DOI: 10.4049/jimmunol.166.11.6555. View