Next Generation γδ T Cell-Based Tumor Immunotherapy

  • 26k

    Total Downloads

  • 90k

    Total Views and Downloads

Download PDFDownload EPUB

Submit your idea

Select the journal/section where you want your idea to be submitted:

Submit your manuscript summarySubmit your manuscript

About this Research Topic

Submission closed

Background

γδ T cells represent an important class of “unconventional” T lymphocytes that play key roles in tumor immunosurveillance. With the increasing recognition of these cells as a clinical correlate for improved disease prognosis, there has been vast interest to harness their unique properties for therapeutic purposes. Seminal studies of Vγ9Vδ2 T cell activation by microbial or endogenous tumor-derived phosphoantigens have set the stage for its applications in targeting tumor. Subsequent discovery of the involvement of butyrophilin/butyrophilin-like proteins in regulating this specific immune reactivity have further paved the way for development of γδ T cell-based therapeutics. Concurrently, advances in understanding the specialized functions of γδ T cell subsets resident in various tissues have provided opportunities for exploiting their unique killing properties against tissue-specific tumors. γδ T cells offer relevant advantages over the conventional T cells: they are not MHC-restricted and they serve as a bridge between innate and adaptive immunity. Further manipulation could result improved anti-tumor immunity.

Although there is extensive evidence that γδ T cells have potent anti-tumor activity, early clinical trials involving ex vivo activation and expansion of endogenous Vγ9Vδ2 T cells by pyrophosphates or aminobisphosphonates (N-BP), such as zoledronic acid followed by their adoptive transfer into tumor patients, have shown limited success in tumor control. More studies are needed to address mechanisms of failure of with the aim to improve γδ T immunotherapy. These may involve investigating specific, context-dependent effects of butyrophilins to mediate activation of Vγ9+ γδ T cells which will inform the development of novel molecules that fine tune intracellular signaling in these cells. More recent research efforts have focused on genetic engineering of γδ T cells to express chimeric antigen receptors (CARs) for redirected anti-tumor reactivity, metabolic reprogramming of their intracellular circuitry to overcome tumor-induced immunosuppression and to promote their capacity to galvanize other immune cell types in anti-tumor responses and long-term maintenance following tumor eradication. Innovations to develop platform technologies for the clinical manufacturing γδ T cells are also expected to be important to support these research initiatives.

In this Research Topic, we welcome the submission of Original Research, Review, Methods articles that focus but are not limited to the following subtopics:
• Different approaches to engineer γδ T cells for tumor immunotherapy: CAR; armored to secrete immunomodulatory, anti-tumor cytokines; metabolic programming to enhance anti-tumor function; development of tumor-infiltrating γδ T cells that locally secrete checkpoint blockade mAbs, BiTEs, etc.
• Metabolic programming of γδ T cells to enhance their anti-tumor function.
• Investigation of which subsets of γδ T cells can be activated to optimize anti-tumoral activity: Vγ9+Vδ2+ (blood: new generation phosphoantigens; aminobisphosphonates such as zoledronic acid; synthetic bisphosphonate pro-drug, pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA), that both expands Vγ9Vδ2 cells and increases their ability to recognize tumor cells; agonistic anti-BTN3A1 antibodies).
• Vδ1+ γδ T cells expressing various Vγ elements (DOT cells) and other Vδ1/2- [such as Vγ4+Vδ5+ (EPCR as γδ TCR ligand) and Vγ8+Vδ3+ (Annexin A2 as γδ TCR ligand)] γδ T cells, both in circulation and various tissues.
• Contextual factors which determine whether γδ T cells are pro-tumoral or anti-tumoral in others.

Keywords: CAR T cells; cancer immunotherapy; immunosurveillance, γδ T Cell

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and it falls under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

    In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Participating Journals

Impact

  • 90kTopic views
  • 62kArticle views
  • 26kArticle downloads
View impact