Activated B-Cells Enhance Epitope Spreading to Support Successful Cancer Immunotherapy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Apr 4

PMID 38571942

Authors

Guillaume Kellermann

Nicolas Leulliot

Julien Cherfils-Vicini

Magali Blaud

Patrick Brest

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint therapies (ICT) have transformed the treatment of cancer over the past decade. However, many patients do not respond or suffer relapses. Successful immunotherapy requires epitope spreading, but the slow or inefficient induction of functional antitumoral immunity delays the benefit to patients or causes resistances. Therefore, understanding the key mechanisms that support epitope spreading is essential to improve immunotherapy. In this review, we highlight the major role played by B-cells in breaking immune tolerance by epitope spreading. Activated B-cells are key Antigen-Presenting Cells (APC) that diversify the T-cell response against self-antigens, such as ribonucleoproteins, in autoimmunity but also during successful cancer immunotherapy. This has important implications for the design of future cancer vaccines.

References

Lynn G, Sedlik C, Baharom F, Zhu Y, Ramirez-Valdez R, Coble V . Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens. Nat Biotechnol. 2020; 38(3):320-332. PMC: 7065950. DOI: 10.1038/s41587-019-0390-x. View

Lam H, McNeil L, Starobinets H, DeVault V, Cohen R, Twardowski P . An Empirical Antigen Selection Method Identifies Neoantigens That Either Elicit Broad Antitumor T-cell Responses or Drive Tumor Growth. Cancer Discov. 2021; 11(3):696-713. DOI: 10.1158/2159-8290.CD-20-0377. View

Ye J, Lee P . B cell receptor signaling strength modulates cancer immunity. J Clin Invest. 2022; 132(6). PMC: 8920327. DOI: 10.1172/JCI157665. View

Sandberg J, Franksson L, Sundback J, Michaelsson J, Petersson M, Achour A . T cell tolerance based on avidity thresholds rather than complete deletion allows maintenance of maximal repertoire diversity. J Immunol. 2000; 165(1):25-33. DOI: 10.4049/jimmunol.165.1.25. View

Leibler C, John S, Elsner R, Thomas K, Smita S, Joachim S . Genetic dissection of TLR9 reveals complex regulatory and cryptic proinflammatory roles in mouse lupus. Nat Immunol. 2022; 23(10):1457-1469. PMC: 9561083. DOI: 10.1038/s41590-022-01310-2. View

Rosenthal R, Cadieux E, Salgado R, Al Bakir M, Moore D, Hiley C . Neoantigen-directed immune escape in lung cancer evolution. Nature. 2019; 567(7749):479-485. PMC: 6954100. DOI: 10.1038/s41586-019-1032-7. View

Sahin U, Oehm P, Derhovanessian E, Jabulowsky R, Vormehr M, Gold M . An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020; 585(7823):107-112. DOI: 10.1038/s41586-020-2537-9. View

Fontaine M, Vogel I, Van Eycke Y, Galuppo A, Ajouaou Y, Decaestecker C . Regulatory T cells constrain the TCR repertoire of antigen-stimulated conventional CD4 T cells. EMBO J. 2017; 37(3):398-412. PMC: 5793804. DOI: 10.15252/embj.201796881. View

Hong S, Zhang Z, Liu H, Tian M, Zhu X, Zhang Z . B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4 T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen. Immunity. 2018; 49(4):695-708.e4. DOI: 10.1016/j.immuni.2018.08.012. View

10.

Kumai T, Lee S, Cho H, Sultan H, Kobayashi H, Harabuchi Y . Optimization of Peptide Vaccines to Induce Robust Antitumor CD4 T-cell Responses. Cancer Immunol Res. 2016; 5(1):72-83. PMC: 5221568. DOI: 10.1158/2326-6066.CIR-16-0194. View

11.

Burchill M, Tamburini B, Kedl R . T cells compete by cleaving cell surface CD27 and blocking access to CD70-bearing APCs. Eur J Immunol. 2015; 45(11):3140-9. PMC: 4674305. DOI: 10.1002/eji.201545749. View

12.

Atsumi S, Katoh H, Komura D, Hashimoto I, Furuya G, Koda H . Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases. Commun Biol. 2020; 3(1):588. PMC: 7567837. DOI: 10.1038/s42003-020-01305-5. View

13.

Petrelli F, Grizzi G, Ghidini M, Ghidini A, Ratti M, Panni S . Immune-related Adverse Events and Survival in Solid Tumors Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. J Immunother. 2019; 43(1):1-7. DOI: 10.1097/CJI.0000000000000300. View

14.

Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S . Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A. 2008; 105(29):10113-8. PMC: 2481354. DOI: 10.1073/pnas.0711106105. View

15.

Chesney J, Puzanov I, Collichio F, Singh P, Milhem M, Glaspy J . Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. J Immunother Cancer. 2023; 11(5). PMC: 10163510. DOI: 10.1136/jitc-2022-006270. View

16.

Bekeredjian-Ding I, Berkeredjian-Ding I, Wagner M, Hornung V, Giese T, Schnurr M . Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN. J Immunol. 2005; 174(7):4043-50. DOI: 10.4049/jimmunol.174.7.4043. View

17.

Anz D, Koelzer V, Moder S, Thaler R, Schwerd T, Lahl K . Immunostimulatory RNA blocks suppression by regulatory T cells. J Immunol. 2009; 184(2):939-46. DOI: 10.4049/jimmunol.0901245. View

18.

Agerer B, Koblischke M, Gudipati V, Montano-Gutierrez L, Smyth M, Popa A . SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8 T cell responses. Sci Immunol. 2021; 6(57). PMC: 8224398. DOI: 10.1126/sciimmunol.abg6461. View

19.

Klarquist J, Cross E, Thompson S, Willett B, Aldridge D, Caffrey-Carr A . B cells promote CD8 T cell primary and memory responses to subunit vaccines. Cell Rep. 2021; 36(8):109591. PMC: 8456706. DOI: 10.1016/j.celrep.2021.109591. View

20.

Buchta C, Bishop G . Toll-like receptors and B cells: functions and mechanisms. Immunol Res. 2014; 59(1-3):12-22. DOI: 10.1007/s12026-014-8523-2. View