Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

Chong, Chloé; Müller, Markus; Pak, HuiSong; Harnett, Dermot; Huber, Florian; Grun, Delphine; Leleu, Marion; Auger, Aymeric; Arnaud, Marion; Stevenson, Brian J.; Michaux, Justine; Bilić, Ilija; Hirsekorn, Antje; Calviello, Lorenzo; Simó-Riudalbas, Laia; Planet, Evarist; Lubiński, Jan; Bryśkiewicz, Marta; Wiznerowicz, Maciej; Xénarios, Ioannis; Zhang, Lin; Trono, Didier; Harari, Alexandre; Ohler, Uwe; Coukos, George; Bassani-Sternberg, Michal

doi:10.1038/s41467-020-14968-9

Cited by 225 publications

(263 citation statements)

References 96 publications

Supporting

Mentioning

230

Contrasting

Order By: Relevance

“…It has been proposed that up to 10% of the MHCI bound peptides can originate from non-coding genomic regions, untranslated regions and exonic out-of-frame translation. Additional sources of cryptic antigens can be long non-coding RNAs, altered mRNA splicing events, small nucleolar RNAs, and proteins encoded in ribosomal DNA [ 197 ]. If one takes into account that 99% of tumor-specific mutations are located in non-coding regions, these cryptic MHCI antigens can be a very rich source of tumor-specific antigens [ 197 , 198 ].…”

Section: Tumor Antigens and Tumor-associated Antigenic Peptidesmentioning

confidence: 99%

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Mpakali

Stratikos

2021

Cancers

View full text Add to dashboard Cite

Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

show abstract

Section: Tumor Antigens and Tumor-associated Antigenic Peptidesmentioning

confidence: 99%

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Mpakali

Stratikos

2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Since cryptic MAPs cannot be identified using canonical protein databases, Laumont et al have recently developed a proteogenomic-based approach to identify both of canonical and cryptic MAPs specific to tumor cells (e.g., mutated and aberrantly expressed TSA) (93). In parallel of this, two proof-ofprinciple studies established that MAPs can also be identified using reference databases built from ribosome profiling (Riboseq) (137,138). Ribo-Seq is based on the sequencing of mRNA fragments protected for ribonuclease digestion by their location within the ribosome decoding site.…”

Section: Tumor-specific Antigen Derived From Aberrant Translationmentioning

confidence: 99%

A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

2020

View full text Add to dashboard Cite

The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.

show abstract

“…In the second approach, normal adjacent tissue (not tumor-infiltrated) is used as a negative control [ 50 ]. Once again, the absence of a MAP in the normal adjacent tissue does not guarantee that it is not present in other cell types in the organism.…”

Section: Strategies For Mass Spectrometry-based Identification Of mentioning

confidence: 99%

The Origin and Immune Recognition of Tumor-Specific Antigens

Apavaloaei

Hardy

Thibault

et al. 2020

Cancers

View full text Add to dashboard Cite

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, it is therefore important to perform mass spectrometry analyses that interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct major histocompatibility complex (MHC) I presentation but poor substrates for cross-presentation. This is an important caveat, because cancer cells are poor antigen-presenting cells, and the immune system, therefore, depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We, therefore, postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs may represent an attractive strategy for cancer treatment.

show abstract

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

Cited by 225 publications

References 96 publications

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

The Origin and Immune Recognition of Tumor-Specific Antigens

Contact Info

Product

Resources

About