About this Research Topic
Neoantigens are tumor-specific antigens derived from somatic genomic aberrations and are drivers of anti-cancer immunity by their presentation to T cells via MHC. Several neoantigen targeting approaches are currently being pursued in the clinic for cancer treatment. These approaches are currently focused on neoantigens derived from somatic mutations like single nucleotide variants, indels, gene fusions, etc. However, there are other sources of potentially tumor-specific antigens, that are derived from cancer-specific dysregulated expression from non-canonical coding regions of the genome, for example from transposable elements, endogenous retroviruses, lncRNAs, UTRs, etc. Even if these may result in non-coding transcripts, they can still be susceptible to intermittent translation and presentation by MHC. These antigens, if tumor-specific, might be targets of anti-tumor immunity.
Identification of such non-canonical transcripts is mostly a recently tackled problem, with several computational approaches recently published that aim to identify these transcripts from RNA-seq data, or Ribo-seq. It’s not clear if these approaches, which include pseudomapping, de novo transcript assembly, etc. identify the same transcripts. Furthermore, with the advent of single-cell expression atlases, there is an opportunity to further understand the tumor specificity of these transcripts, within the limitations of single-cell approaches to identify such transcripts.
The goal of this Research Topic is to address several questions relating to the utility of these elements as therapeutic targets, and their role in anti-tumor immunity:
• How tumor-specific are these transcripts? Do single-cell studies throw more light on this compared with bulk-RNA seq studies?
• What is their role in inducing an inflammatory environment (by recognition by innate sensing of these elements)?
• Do we see functionally relevant T cell responses against these elements?
In this Research Topic, we welcome the submission of Original Research, Systematic Review, Review, Mini Review, Clinical Trial, Opinion, and Perspective articles covering but not limited to the following sub-topics:
• Bulk and single-cell RNA seq studies on identifying non-coding transcripts, and MHC-presented ligands from such transcripts in tumors or even normal cell types.
• Studies on innate sensing of endogenous retroviruses, and the relevance of such sensing to antigen presentation in cancer.
• Modulation of the tumor microenvironment by these non-canonical antigens in tumor models.
• Relevance of these viral mimicking antigens in cancers driven by oncoviruses.
• Methods for identification of noncoding transcripts from single-cell data
NOTE: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic Editors Hang Xu and Suchit Jhunjhunwala are currently employed by Genentech. Topic Editor Stephane Depil is the founder and chairman of ErVaccine Technologies.
Identification of such non-canonical transcripts is mostly a recently tackled problem, with several computational approaches recently published that aim to identify these transcripts from RNA-seq data, or Ribo-seq. It’s not clear if these approaches, which include pseudomapping, de novo transcript assembly, etc. identify the same transcripts. Furthermore, with the advent of single-cell expression atlases, there is an opportunity to further understand the tumor specificity of these transcripts, within the limitations of single-cell approaches to identify such transcripts.
The goal of this Research Topic is to address several questions relating to the utility of these elements as therapeutic targets, and their role in anti-tumor immunity:
• How tumor-specific are these transcripts? Do single-cell studies throw more light on this compared with bulk-RNA seq studies?
• What is their role in inducing an inflammatory environment (by recognition by innate sensing of these elements)?
• Do we see functionally relevant T cell responses against these elements?
In this Research Topic, we welcome the submission of Original Research, Systematic Review, Review, Mini Review, Clinical Trial, Opinion, and Perspective articles covering but not limited to the following sub-topics:
• Bulk and single-cell RNA seq studies on identifying non-coding transcripts, and MHC-presented ligands from such transcripts in tumors or even normal cell types.
• Studies on innate sensing of endogenous retroviruses, and the relevance of such sensing to antigen presentation in cancer.
• Modulation of the tumor microenvironment by these non-canonical antigens in tumor models.
• Relevance of these viral mimicking antigens in cancers driven by oncoviruses.
• Methods for identification of noncoding transcripts from single-cell data
NOTE: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic Editors Hang Xu and Suchit Jhunjhunwala are currently employed by Genentech. Topic Editor Stephane Depil is the founder and chairman of ErVaccine Technologies.
Keywords: ERV, hERV, LTR, neoantigens, nuORFs, MHC, HLA, cancer, non coding, antigens, immunotherapy, endogenous retroviruses
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.
