Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Hindawi Limited full text link Hindawi Limited Free PMC article
Full text links

Actions

Share

Review
.2015:2015:948501.
doi: 10.1155/2015/948501. Epub 2015 Jun 16.

Human Tumor Antigens and Cancer Immunotherapy

Affiliations
Review

Human Tumor Antigens and Cancer Immunotherapy

Nathalie Vigneron. Biomed Res Int.2015.

Abstract

With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Tumor antigens recognized by cytolytic T lymphocytes. Tumor antigens are classified according to the pattern of expression of the parental gene. The production of antigenic peptides by cancer cells (upper panel) and healthy cells (lower panel) is depicted. Viral antigens are only expressed in virally infected cells. Mutated genes can give rise to a modified peptide that is able to bind the HLA class I molecules while the wild-type peptide cannot (left). The mutation can also alter a peptide, which is able to bind the HLA class I molecule, so that this modified peptide is now recognized as nonself by circulating CTL. Cancer-germline genes are expressed in tumors or germline cells as a result of whole genome demethylation. MAGE-type antigens encoded by cancer-germline genes are not expressed at the surface of healthy cells nor on germline cells since the latter do not express HLA class I molecules. Differentiation antigens are encoded by genes with a tissue-specific expression. They are therefore expressed by some types of tumors and the corresponding healthy tissue. Some genes are overexpressed in tumors as a result of increased transcription or gene amplification. The resulting peptides are highly expressed on these tumors but also show a low level of expression in some or all healthy tissues.
Figure 2
Figure 2
Processing of tumor antigens recognized by CD8+ T cells. CTL recognize peptides that are produced by the degradation of cellular proteins by the proteasome. Four types of proteasome exist, two of which are represented here (standard proteasome and immunoproteasome). Peptides resulting from proteasome degradation are then transported in the lumen of the ER by the TAP transporter. Peptides bearing an extended N-terminus can be further trimmed by additional proteases such as ERAP1 before being loaded on HLA class I molecules with the help of the peptide loading complex, which is composed of TAP, tapasin (Tpn), the oxidoreductase ERp57, and the chaperone calreticulin (CRT). Peptide/HLA complexes are then transferred to the cell surface through the secretory pathway.
Figure 3
Figure 3
Proteasome activities. (a) Peptide-bond hydrolysis. In the course of peptide-bond hydrolysis, the hydroxyl group of the N-terminal threonine produces a nucleophile attack on the carbonyl of the peptide bond. This leads to the formation of an acyl-enzyme intermediate in which a peptide fragment remains attached to the proteasome through an ester link. Finally hydrolysis of the acyl-enzyme intermediate by a water molecule present in the proteasome chamber will restore the hydroxyl group of the catalytic threonine and release the peptide. (b) Peptide splicing by the proteasome. Splicing of the antigenic peptide RTK_QLYPEW derived from the differentiation antigen gp100. After formation of the acyl-enzyme intermediate involving the fragment RTK, the free N-terminal amino-group of peptide QLYPEW present in the proteasome chamber performs a nucleophilic attack on the acyl-enzyme intermediate. This leads to the creation of a new peptide bond, which assembles both fragments of the spliced peptide. Balls represent the catalyticβ subunits of the proteasome. The hydroxyl group of the N-terminal threonine is indicated.
Figure 4
Figure 4
Proteasome subtypes. Mammalian 20S proteasomes are composed four stacked rings of seven subunits each. The two outer rings are made ofα-subunits and delimit the entrance of the catalytic chamber. The two inner rings are made ofβ subunits, three of which (β1,β2, andβ5) are catalytically active. In immune cells or upon induction with IFNγ, catalytic subunitsβ1,β2, andβ5 are replaced with their inducible counterpartsβ1i,β2i, andβ5i to form immunoproteasomes. Besides standard and immunoproteasomes, two additional forms of proteasome exist, which contain a mixture of standard and immune catalytic subunits, as indicated. The processing ability of these four types of proteasomes was studied for the indicated peptides (lower part of the figure). ++: efficiently produced, +/−: slightly produced, and −: not produced.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hodi F. S., O'Day S. J., McDermott D. F., et al. Improved survival with ipilimumab in patients with metastatic melanoma. The New England Journal of Medicine. 2010;363(8):711–723. doi: 10.1056/nejmoa1003466. - DOI - PMC - PubMed
    1. Robert C., Thomas L., Bondarenko I., et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. The New England Journal of Medicine. 2011;364(26):2517–2526. doi: 10.1056/nejmoa1104621. - DOI - PubMed
    1. Topalian S. L., Hodi F. S., Brahmer J. R., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England Journal of Medicine. 2012;366(26):2443–2454. doi: 10.1056/nejmoa1200690. - DOI - PMC - PubMed
    1. Topalian S. L., Drake C. G., Pardoll D. M. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Current Opinion in Immunology. 2012;24(2):207–212. doi: 10.1016/j.coi.2011.12.009. - DOI - PMC - PubMed
    1. Brahmer J. R., Tykodi S. S., Chow L. Q. M., et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. The New England Journal of Medicine. 2012;366(26):2455–2465. doi: 10.1056/nejmoa1200694. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

Full text links
Hindawi Limited full text link Hindawi Limited Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp