About this Research Topic

Background

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising approach for the treatment of hematologic malignancies. CAR T cells are engineered to express constructs encoding an extracellular antigen-specific recognition sequence fused to a transmembrane domain and intracellular co-stimulatory domain(s) enabling recognition and cytotoxicity against antigen-expressing cells. Best responses to CAR T-cell therapy are associated with several parameters such as the quality of the circulating T cells used for manufacturing, rapid CAR T-cell expansion processes to avoid exhaustion before administration, the systemic level of homeostatic cytokine after lymphodepleting chemotherapy, and evidence of anti-tumor activity typically evaluated by PET-CT 30 days after infusion. Yet, the lack of robust pre-treatment biomarkers for patient stratification and monitoring remains a major challenge. The prognostic and predictive roles of the tumor microenvironment (TME) have been described for solid tumors, including for checkpoint inhibitors, but the systematic analysis of hematopoietic tumors and the role of systemic immune dysregulation in response to CAR T-cell therapy are still at an early stage.

Unlike other therapies, the efficacy of CAR T cell therapy is comparable across all subtypes of Large B-Cell Lymphoma (LBCL) as defined through conventional tumor-related prognostic markers from histological, cytogenetic, or molecular origins. However, recent publications suggest that the response to CAR-T cell therapy also associates with specific characteristics of the systemic immunity and of the tumor immune infiltrates before lymphodepletion. In addition, it is now well documented that both cancer-cell intrinsic and extrinsic features can modulate cancer immune responsiveness. Considering the immune mechanistic nature of the CAR T-cell intervention, host features such as functional status of tumor-infiltrating immune or stroma cells could enable the discovery of novel prognostic biomarkers or therapeutic strategies to improve patient response to CAR T cells. We thus propose to develop a Research Topic investigating the host features that can modulate the response of patients with hematological malignancies to CAR T cell therapy, including TME characteristics (immune tumor signature, DLBCL-activated fibroblastic reticular cells); TME evolution across chemotherapeutic lines; upregulation of circulating immunosuppressive cells; and germline genetic variants.

The Research Topic focuses on host-intrinsic features that can modulate the therapeutic response to CAR T-cells, including:

• functional characteristics of systemic immune cells (such as for example the presence of circulating M-MDSC that associates to therapeutic resistance) and tumor-infiltrating immune cells (including tumor IFN signaling; tumor immune contexture and evolution of TME composition across chemotherapeutic lines and consequences for response to CAR T cell therapeutic response);

• characterization and role of tumor-infiltrating stroma cells (DLBCL-activated fibroblastic reticular cells that hinder T cell migration and cytotoxicity in an antigen-specific manner);

• germline genetics of the tumor immune microenvironment of hematological cancers (LBCL) that may associated to response to CAR T cell therapy.

The use of novel technical approaches to investigate the TME, including but not only spatial transcriptomics and proteomics, and single cell transcriptomics, are of particular interest.


Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.



Dr. Nathalie Scholler is Vice President of TORL Biotherapeutics, a biotech company that develops novel antibody-based therapeutics to treat cancer patients.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: CAR-cell therapy, TME, TIL, fibroblastic reticular cells, myeloid-derived suppressive cells, germline genetic variants

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.

Frequently asked questions

• What is a Research Topic?

  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.

• Why does Frontiers publish Research Topics? 

  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.

• Why are Research Topics important for journals?

  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.

• How do we ensure the quality of articles within Research Topics?

  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.

• What are the benefits of publishing my article in a Research Topic?

  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.

   
• What types of articles can be published in a Research Topic?

  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 

• Can I suggest a new Research Topic? 

  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 

• Who leads a Research Topic? 

  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.

• What is the role of a topic editor?

  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.

• What support will I receive when editing a new Research Topic? 

  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).

• As a junior researcher, can I be involved in editing a Research 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. 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.

• Can I get a certificate for editing a Research Topic?

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

• Who will I collaborate with?

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

• How long does it take to publish a Research Topic?

  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

• What fee support is available to authors publishing in a Research Topic?

  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.

• Will there be a printed version of my Research Topic?

  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.