Review

The dawn of vaccines for cancer prevention

Published online:

Abstract

An important role of the immune system is in the surveillance for abnormal or transformed cells, which is known as cancer immunosurveillance. Through this process, the first changes to normal tissue homeostasis caused by infectious or other inflammatory insults can be detected by the immune system through the recognition of antigenic molecules (including tumour antigens) expressed by abnormal cells. However, as they develop, tumour cells can acquire antigenic and other changes that allow them to escape elimination by the immune system. To bias this process towards elimination, immunosurveillance can be improved by the administration of vaccines based on tumour antigens. Therapeutic cancer vaccines have been extensively tested in patients with advanced cancer but have had little clinical success, which has been attributed to the immunosuppressive tumour microenvironment. Thus, the administration of preventive vaccines at pre-malignant stages of the disease holds promise, as they function before tumour-associated immune suppression is established. Accordingly, immunological and clinical studies are yielding impressive results.

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Acknowledgements

O.J.F. acknowledges support from the US National Institutes of Health, US National Cancer Institute, grant R35CA210039.

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Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

    • Olivera J. Finn

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The author declares no competing financial interests.

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Correspondence to Olivera J. Finn.

Glossary

Checkpoint inhibitors

Antibodies or other drugs that inhibit the function of specific molecules (such as cytotoxic T lymphocyte antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1)) expressed on the surface of immune cells or cancer cells that serve as breaks or that keep immune responses in check at particular time points (checkpoints) in immune cell activation. Blocking the function of these molecules releases the breaks and can lead to tumour destruction.

Engineered T cells

T cells that have been modified ex vivo through gene transfer to assume new functions. For example, T cells can be transduced either with chimeric antigen receptors or with T cell receptors, which endows them with different antigen specificity from that of their endogenous T cell receptors.

Myeloid-derived suppressor cells

(MDSCs). A group of immature myeloid cells (including precursors of macrophages, granulocytes and dendritic cells) that are produced in response to various tumour-derived cytokines. These cells have been shown to induce tumour-associated antigen-specific CD8+ T cell tolerance and to suppress other immune effector cells.

Tumour-associated macrophages

Cells that are an important component of the tumour microenvironment. They differentiate from circulating blood monocytes that have infiltrated tumours. They can have positive or negative effects on tumorigenesis (that is, tumour promotion or immunosurveillance, respectively).

Exhausted phenotype

The condition of functionally impaired antigen-specific T cells, typified by increased surface expression of programmed cell death protein 1 (PD1), which occurs in the context of persistent high antigen load. The defects in effector T cell function include a progressive decrease in their ability to produce cytokines, loss of proliferative capacity and decreased cytotoxicity, and these defects can result in apoptotic cell death.

Tamoxifen

A drug used for the prevention of oestrogen receptor (ER)-positive breast cancer. Tamoxifen is a pro-drug that is metabolized in the liver into active metabolites that have a high affinity for the ER and can compete with endogenous oestrogen.

Monoclonal gammopathy of undetermined significance

(MGUS). A medical condition characterized by the presence of abnormal immunoglobulins and expanded clones of plasma cells that can progress to multiple myeloma, thus requiring periodic surveillance.

Immunoediting

A process by which the immune system of a host may alter the gene expression of an emerging tumour such that the most immunogenic epitopes are removed or edited, thereby facilitating tumour escape from immune recognition.