Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Origin and Immune Recognition of Tumor-Specific Antigens

Version 1 : Received: 27 August 2020 / Approved: 30 August 2020 / Online: 30 August 2020 (10:30:50 CEST)

A peer-reviewed article of this Preprint also exists.

Apavaloaei, A.; Hardy, M.-P.; Thibault, P.; Perreault, C. The Origin and Immune Recognition of Tumor-Specific Antigens. Cancers 2020, 12, 2607. Apavaloaei, A.; Hardy, M.-P.; Thibault, P.; Perreault, C. The Origin and Immune Recognition of Tumor-Specific Antigens. Cancers 2020, 12, 2607.

Journal reference: Cancers 2020, 12, 2607
DOI: 10.3390/cancers12092607

Abstract

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, mass spectrometry analyses must therefore 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 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 represent an attractive strategy for cancer treatment.

Subject Areas

antigen processing and presentation; cancer immunotherapy; cross-priming; immunogenicity; major histocompatibility complex; T lymphocyte; tumor-infiltrating lymphocytes, tumor microenvironment; tumor-specific antigen

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