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Immune evasion in human papillomavirus-associated cervical cancer

Nature Reviews Cancer volume 2, pages 59–64 (2002)Cite this article

Abstract

Tumour-associated viruses produce antigens that, on the face of it, are ideal targets for immunotherapy. Unfortunately, these viruses are experts at avoiding or subverting the host immune response. Cervical-cancer-associated human papillomavirus (HPV) has a battery of immune-evasion mechanisms at its disposal that could confound attempts at HPV-directed immunotherapy. Other virally associated human cancers might prove similarly refractive to immuno-intervention unless we learn how to circumvent their strategies for immune evasion.

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Figure 1: The biology of HPV infection.
Figure 2: How the adaptive immune system 'sees' and responds to tumour (or other foreign) antigens inside cells.
Figure 3: Protective specific immunity to E7 epithelial tumour antigen by administration of an inflammatory stimulus.
Figure 4: E7 in peripheral epithelium tolerizes the CTL response.

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Acknowledgements

The author thanks R. Thomas for helpful discussion.

Author information

Authors and Affiliations

  1. the Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston Road, Herston, 4201, QLD, Australia

    Robert W. Tindle

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  1. Robert W. Tindle
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DATABASES

CancerNet:

Burkitt's lymphoma

Hodgkin's lymphomas

cancer of the uterine cervix

 GenBank:

E6

E7

EBV

HBV

HPV16

 LocusLink:

B7

CD28

IFN-α

IFN-β

IFN-γ

IL-1

IL-1β

IL-10

IL-12

IL-13

IL-18

p53

RB

transforming growth factor-β

tumour necrosis factor-α

FURTHER READING

A Brief Guide to the Immunology of Peripheral Tolerance

Antitumour Immune Response and Cancer Vaccination: The Critical Role of Dendritic Cells

Schematic representation of cervical neoplasia: animated

Tolerance web site

Glossary

ADJUVANT

Any substance that nonspecifically enhances the immune response to antigen.

ALLOGENEIC

Inter-individual genetic variation at the MHC locus. In the semi-allogeneic situation reported in this article, MHC antigens are shared by donor and recipient, but in addition the donor has some MHC antigens that the recipient does not

ANERGY

A state in which T cells cannot respond to antigen.

ANTIGEN-PRESENTING CELLS (APCs)

Cells that process antigen and present antigen fragments to other cells of the immune system (cross-presentation) to initiate an immune response. Dendritic cells are the most potent APCs.

CD4 HELP

The secretion of cytokines, particularly interleukin-2, that are necessary for the expression of effector function by other cells in the immune system, especially CD8+ T cells.

CD40 LIGAND

A molecule on CD4+ T cells that, when it binds CD40 on dendritic cells, stimulates them to mature.

CD8+ T CELL

T cell bearing the CD8+ cell-surface glycoprotein, which recognizes MHC class I molecules on target cells. CD8+ T cells are usually cytotoxic T cells.

CONDYLOMA

Papillomavirus-associated soft wart on genital mucosal epithelium.

DECOY CYTOKINE

A molecule encoded by the genome of an invading organism that mimics the effect of a host cytokine and manipulates the immune response to the invader's advantage.

EARLY PROTEINS

Gene products translated from the first mRNAs that are produced from the viral genome, before viral replication gets underway.

GENITAL HYPERPLASIA

Dysregulated proliferation of keratinocytes of genital epithelium.

LANGERHANS CELLS

A subset of antigen-presenting cells in the epithelium.

LATE PROTEINS.

After viral DNA replication, 'late' viral genes become available for transcription. Their mRNAs encode structural proteins (L1 and L2 in HPV), which form the capsids of new virions.

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

A genetic region encoding proteins that are involved in antigen presentation to T cells. MHC class I molecules bound to peptide are recognized by the T-cell receptors of CD8+ T cells.

MATURATION OF DENDRITIC CELLS

A process that is instigated by inflammatory cytokines, in which dendritic cells acquire co-stimulatory molecules that allow them to interact with and transmit activating signal(s) to specific T cells.

NATURAL KILLER (NK) CELLS

Large granular lymphocytes that do not bear a T-cell receptor, but can recognize and destroy certain tumour cells and virally infected cells in an MHC-independent manner.

REDUNDANCY IN THE GENETIC CODE

Several nucleotide triplets can encode the same amino acid and, correspondingly, several tRNAs are observed for that amino acid. Differences in abundance of different tRNAs are observed between species and sometimes between tissues in the same species.

SYNGENEIC

Genetically identical, for example, a fully inbred strain of mouse.

TRANSPORTER ASSOCIATED WITH ANTIGEN PROCESSING (TAP)

The peptide products of protein degradation in cytoplasm are transported by TAP molecules to the endoplasmic reticulum where they are loaded onto MHC molecules.

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Tindle, R. Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer 2, 59–64 (2002). https://doi.org/10.1038/nrc700

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