Genetic Variants as Targets for Immunotherapy of Hematological Tumors

  • 23k

    Total downloads

  • 84k

    Total views and downloads

Download PDFDownload EPUB

About this Research Topic

Submission closed

Background

Over the past decades, patients with leukemia and other hematological malignancies have been successfully treated with allogeneic hematopoietic stem cell transplantation. The anti-tumor effect of this treatment is mediated by donor T cells targeting HLA-peptide complex disparities between patient and donor. These differences are encoded in the germline and thus ubiquitously present on patient cells. Therefore, donor T cells targeting polymorphic HLA-peptide complexes after allogeneic stem cell transplantation cause not only beneficial anti-tumor or Graft-versus-Leukemia (GvL) reactivity, but also respond against healthy tissues leading to undesired Graft-versus-Host-Disease (GvHD).

Germline polymorphisms that are targeted after allogeneic stem cell transplantation can reside in genes encoding the HLA surface molecule or in genes encoding its presented peptide. Donor T cell responses against patient-specific mismatched HLA alleles are often very strong, thereby causing severe GvHD and negatively affecting treatment outcome. Therefore, to limit GvHD, patients are preferably transplanted with HLA-matched donors. After HLA-matched allogeneic stem cell transplantation, allogeneic donor T cell responses still exist, targeting polymorphic peptides presented by HLA molecules that are shared between patient and donor. In 1995, the first polymorphic HLA-binding peptide or minor histocompatibility antigen was identified. Since then, the discovery and knowledge of minor histocompatibility antigens and their specific T cells rapidly accelerated. This knowledge has proven to be essential to understand and manipulate the delicate balance of GvL and GvHD after allogeneic stem cell transplantation.

The characterization of minor histocompatibility antigens also illustrated that cancer can be cured by T cells targeting HLA-binding peptides encoded by genetic variants that are absent in the thymus where the T cells have been educated. This has been confirmed by the finding that neoantigens, which are HLA-binding peptides created by somatic mutations, can be targeted in non-transplanted cancer patients. T cells recognizing neoantigens have a high affinity and strong capacity to selectively kill tumor cells over healthy cells. Moreover, immunotherapy induced or stimulated neoantigen-specific T cells, which are often found in patients with a high number of somatic mutations in their cancer cells, can induce long-term clinical remissions. Although hematological malignancies often have a low mutational load, neoantigens can be presented on these tumors and provide attractive targets for immunotherapy. Their relevance as immunotherapeutic targets have recently been demonstrated by the isolation of a T cell receptor for mutant NPM1. NPM1 is mutated in 30-35% of patients with acute myeloid leukemia and the T cell receptor can be used to specifically target leukemic cells and treat these patients with gene therapy.

We welcome Original Research, Review, Method, Systematic Review, Mini-Review, Hypothesis and Theory, Perspective, Clinical Trial, Case Reports, Classification, Opinion and Technology & Code articles that cover the following themes:

1. Prediction and discovery of minor histocompatibility antigens.
2. Detection and manipulation of T cells for minor histocompatibility antigens.
3. Prediction and discovery of neoantigens on hematological malignancies.
4. Detection and stimulation of T cells for neoantigens on hematological malignancies.
5. Association of minor histocompatibility antigens or neoantigens with disease or treatment response.

Keywords: minor histocompatibility antigens, neoantigens, hematological malignancies, allogeneic stem cell transplantation, immunotherapy

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

  • 84kTopic views
  • 59kArticle views
  • 23kArticle downloads
View impact