Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies

Article Immunology

Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer

Antonela Merlotti et al.

Summary: Noncanonical mRNA splicing events can encode recurrent and immunogenic tumor-specific antigens in NSCLC patients.

SCIENCE IMMUNOLOGY (2023)

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Article Biotechnology & Applied Microbiology

Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer

Tamara Ouspenskaia et al.

Summary: Peptides originating from novel or unannotated open reading frames (nuORFs) detected by ribosome profiling can be displayed on MHC-I of cancer cells, serving as additional sources of cancer antigens. These nuORFs represent an unexplored pool of tumor-specific peptides with potential as immunotherapy targets.

NATURE BIOTECHNOLOGY (2022)

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Article Biochemistry & Molecular Biology

SPENCER: a comprehensive database for small peptides encoded by noncoding RNAs in cancer patients

Xiaotong Luo et al.

Summary: The SPENCER database compiles research on ncRNA-encoded small peptides in cancer, identifying 29,526 ncPEPs across 15 different cancer types. Of these, 22,060 have been experimentally validated. Additionally, SPENCER predicted the immunogenicity of 4497 ncPEPs, making it a valuable resource for cancer research.

NUCLEIC ACIDS RESEARCH (2022)

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Article Oncology

Cancer-related micropeptides encoded by ncRNAs: Promising drug targets and prognostic biomarkers

Sarra Setrerrahmane et al.

Summary: Micropeptides, short peptides with less than 100 amino acids, have been discovered in the field of noncoding RNA. They are suggested to play essential regulatory roles in various physiological and pathological processes. Genomics studies have revealed that these micropeptides are encoded by concealed small open reading frames within misannotated ncRNAs, such as lncRNAs and circRNAs. Despite their contributions to tumorigenesis, little is known about the pathological mechanisms of these ncRNA-encoded micropeptides due to challenges in identifying translated sORFs.

CANCER LETTERS (2022)

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Article Biochemical Research Methods

MHC Class I Immunopeptidome: Past, Present, and Future

Jonathan W. Yewdell

Summary: In the past 35 years, significant progress has been made in the study of immunopeptidome, revealing the importance of short peptides binding to major histocompatibility complex in T-cell recognition. This article discusses the contribution of proteasome-mediated splicing to immunopeptidome and the recent findings linking immunopeptidome to the translatome revealed by ribosome profiling. It also emphasizes the need to attract talented young scientists to further advance antigen-processing research, which has seen remarkable success in T-cell-based cancer immunotherapy.

MOLECULAR & CELLULAR PROTEOMICS (2022)

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Meeting Abstract Oncology

UNCOVERING THE DARK IMMUNOPEPTIDOME OF HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC): RELEVANCE FOR UNIVERSAL CANCER VACCINES, IMMUNOLOGICAL MONITORING AND TIL THERAPY

Noriko Iwamoto et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Cell Biology

Most non-canonical proteins uniquely populate the proteome or immunopeptidome

Maria Virginia Ruiz Cuevas et al.

Summary: By combining RNA sequencing, ribosome profiling, and mass spectrometry, the study reveals the significant contribution of non-canonical translation to the proteome and MHC class I immunopeptidome. It identifies a large number of cryptic proteins and shows their high efficiency in generating MHC-I peptides.

CELL REPORTS (2021)

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Article Immunology

Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes

Gregory Ehx et al.

Summary: An analysis of the immunopeptidome in AML patients identified tumor-specific antigens (TSAs) which were derived from non-coding genomic regions and associated with intron retention and epigenetic changes. These TSAs may serve as attractive targets for AML immunotherapy.

IMMUNITY (2021)

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Review Immunology

A few good peptides: MHC class I-based cancer immunosurveillance and immunoevasion

Devin Dersh et al.

Summary: In this review, the authors discuss the impact of dysregulated protein translation in cancer cells on immunosurveillance, as well as how tumors manipulate antigen-processing pathways for immune evasion. Additionally, they highlight two limiting factors in the application of CD8(+)T cell immunotherapies.

NATURE REVIEWS IMMUNOLOGY (2021)

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Article Multidisciplinary Sciences