Potential use of gamma delta T cell-based vaccines in cancer immunotherapy

Article English OPEN
Khan, Mohd Wajid A. ; Eberl, Matthias ; Moser, Bernhard
  • Publisher: Frontiers Research Foundation
  • Subject: RC0254 | QR180 | RM

Immunotherapy is a fast advancing methodology involving one of two approaches: (1) compounds targeting immune checkpoints and (2) cellular immunomodulators. The latter approach is still largely experimental and features in vitro generated, live immune effector cells, or antigen-presenting cells. γδ T cells are known for their efficient in vitro tumor killing activities. Consequently, many laboratories worldwide are currently testing the tumor killing function of γδ T cells in clinical trials. Reported benefits are modest; however, these studies have demonstrated that large γδ T-cell infusions were well tolerated. Here, we discuss the potential of using human γδ T cells not as effector cells but as a novel cellular vaccine for treatment of cancer patients. Antigen-presenting γδ T cells do not require to home to tumor tissues but, instead, need to interact with endogenous, tumor-specific αβ T cells in secondary lymphoid tissues. Newly mobilized effector αβ T cells are then thought to overcome the immune blockade by creating proinflammatory conditions fit for effector T-cell homing to and killing of tumor cells. Immunotherapy may include tumor antigen-loaded γδ T cells alone or in combination with immune checkpoint inhibitors.
  • References (47)
    47 references, page 1 of 5

    1. Moser B, Eberl M. gammadelta T cells: novel initiators of adaptive immunity. Immunol Rev (2007) 215:89-102. doi:10.1111/j.1600-065X.2006.00472.x

    2. Morita CT, Jin C, Sarikonda G, Wang H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev (2007) 215:59-76. doi:10.1111/j.1600-065X.2006. 00479.x

    3. Riganti C, Massaia M, Davey MS, Eberl M. Human gammadelta T-cell responses in infection and immunotherapy: common mechanisms, common mediators? Eur J Immunol (2012) 42:1668-76. doi:10.1002/eji.201242492

    4. Moser B, Loetscher P. Lymphocyte traffic control by chemokines. Nat Immunol (2001) 2:123-8. doi:10.1038/84219

    5. Bromley SK, Mempel TR, Luster AD. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol (2008) 9:970-80. doi:10. 1038/ni.f.213

    6. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med (2000) 192:1545-52. doi:10.1084/jem.192.11.1545

    7. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med (2000) 192:1553-62. doi:10.1084/jem.192.11.1553

    8. Brandes M, Willimann K, Lang AB, Nam KH, Jin C, Brenner MB, et al. Flexible migration program regulates gamma delta T-cell involvement in humoral immunity. Blood (2003) 102:3693-701. doi:10.1182/blood-2003-04-1016

    9. Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol (2000) 18:593-620. doi:10.1146/annurev.immunol.18.1.593

    10. Caccamo N, Battistini L, Bonneville M, Poccia F, Fournié JJ, Meraviglia S, et al. CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production. J Immunol (2006) 177:5290-5. doi:10.4049/jimmunol.177.8.5290

  • Metrics
    views in OpenAIRE
    views in local repository
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Online Research @ Cardiff - IRUS-UK 0 32
Share - Bookmark