Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion

Jhunjhunwala, Suchit; Hammer, Christian; Delamarre, Lélia

doi:10.1038/s41568-021-00339-z

Cited by 743 publications

(579 citation statements)

References 202 publications

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“…Full scan mass spectra (350-1200 m/z, 60,000 resolution) were detected in the orbitrap analyzer after accumulation of 3E6 ions (normalized AGC target of 300%), automatic maximum injection time (IT). For every full scan, MS 2 spectrum were collected during a 3 second cycle time. Ions were isolated (0.4 m/z isolation width) for a maximum IT of 150/250 ms or 1E5/7.5E4 ions (100%/75% normalized AGC target) and fragmented by HCD with 30% collision energy at a resolution of 60,000.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models

Stopfer

Sanders

et al. 2021

Preprint

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Effective immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex Class I (MHC-I). Recent developments in proteomics have improved the identification of peptides that are naturally presented by MHC-I, collectively known as the “immunopeptidome”. Current approaches to profile tumor immunopeptidomes have been limited to in vitro investigation, which fails to capture the in vivo repertoire of MHC-I peptides, or bulk tumor lysates, which are obscured by the lack of tumor-specific MHC-I isolation. To overcome these limitations, we report here the engineering of a Cre recombinase-inducible affinity tag into the endogenous mouse MHC-I gene and targeting of this allele to the KrasLSL-G12D/+; p53fl/fl (KP) mouse model (KP; KbStrep). This novel approach has allowed us to isolate tumor-specific MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAD) in vivo. With this powerful analytical tool, we were able to profile the evolution of the LUAD immunopeptidome through tumor progression and show that in vivo MHC-I presentation is shaped by post-translational mechanisms. We also uncovered novel, putative LUAD tumor associated antigens (TAAs). Many peptides that were recurrently presented in vivo exhibited very low expression of the cognate mRNA, provoking reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance. Beyond cancer, the KbStrep allele is compatible with a broad range of Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease, and autoimmunity.

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Section: Methodsmentioning

confidence: 99%

Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models

Stopfer

Sanders

et al. 2021

Preprint

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“…DCs can take up cancer antigens at the tumor site or in the draining lymph node (LN). Subsequently, DCs process and present these antigens in their MHC molecules, MHC class I or II to elicit responses by CD8 + or CD4 + T cells, respectively [ 26 , 27 ]. MHC class I is present on all nucleated cells and is usually loaded with endogenous peptides derived from the cytosol.…”

Section: Antigen and Adjuvant Are The Basic Ingredients Of Vaccinesmentioning

confidence: 99%

Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines

et al. 2021

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Liposomes have emerged as interesting vehicles in cancer vaccination strategies as their composition enables the inclusion of both hydrophilic and hydrophobic antigens and adjuvants. In addition, liposomes can be decorated with targeting moieties to further resemble pathogenic particles that allow for better engagement with the immune system. However, so far liposomal cancer vaccines have not yet reached their full potential in the clinic. In this review, we summarize recent preclinical studies on liposomal cancer vaccines. We describe the basic ingredients for liposomal cancer vaccines, tumor antigens, and adjuvants, and how their combined inclusion together with targeting moieties potentially derived from pathogens can enhance vaccine immunogenicity. We discuss newly identified antigen-presenting cells in humans and mice that pose as promising targets for cancer vaccines. The lessons learned from these preclinical studies can be applied to enhance the efficacy of liposomal cancer vaccination in the clinic.

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“…As a result, components of the MHC‐I pathway are often directly targeted by viruses to avoid immune recognition (Schuren et al., 2016). Furthermore, defects in the components of the MHC‐I APP pathway often arise in tumours, offering a selective advantage in the context of an anti‐tumour T‐cell response (Dersh et al., 2021; Friedrich et al., 2019; Jhunjhunwala et al., 2021; Leone et al., 2013). Such defects are frequently associated with increased metastasis and reduced patient survival.…”

Section: The Impact Of Defects In the Antigen Processing And Presentation Pathwaymentioning

confidence: 99%

Polymorphisms in MHC class I molecules influence their interactions with components of the antigen processing and presentation pathway

Aflalo

Boyle

2021

Int J Immunogenetics

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MHC class I (MHC‐I) molecules undergo an intricate folding process in order to pick up antigenic peptide to present to the immune system. In recent years, the discovery of a new peptide editor for MHC‐I has added an extra level of complexity in our understanding of how peptide presentation is regulated. On top of this, the incredible diversity in MHC‐I molecules leads to significant variation in the interaction between MHC‐I and components of the antigen processing and presentation pathway. Here, we review our current understanding regarding how polymorphisms in human leukocyte antigen class I molecules influence their interactions with key components of the antigen processing and presentation pathway. A deeper understanding of this may offer new insights regarding how apparently subtle variation in MHC‐I can have a significant impact on susceptibility to disease.

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Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion

Cited by 743 publications

References 202 publications

Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models

Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models

Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines

Polymorphisms in MHC class I molecules influence their interactions with components of the antigen processing and presentation pathway

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