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Immunotherapy of autoimmunity and cancer: the penalty for success

Nature Reviews Immunology volume 8, pages 970–976 (2008)Cite this article

Abstract

Advances in our understanding of autoimmunity and tumour immunity have led to improvements in immunotherapy for these diseases. Ironically, effective tumour immunity requires the induction of the same responses that underlie autoimmunity, whereas autoimmunity is driven by dysregulation of the same mechanisms that are involved in host defence and immune surveillance. Therefore, as we manipulate the immune system to treat cancer or autoimmunity, we inevitably unbalance the vital mechanisms that regulate self tolerance and antimicrobial resistance. This Science and Society article aims to dissect the conundrum that is inherent to the concept of immunotherapy and highlights the need for new and more specific therapeutic approaches.

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Figure 1: A simplified model of common immune responses following adoptive immunotherapy.
Figure 2: Severe vitiligo and uveitis induced by adoptive immunotherapy for melanoma.

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Acknowledgements

The author's work is funded by the National Institutes of Health Intramural Program.

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Authors and Affiliations

  1. Rachel R. Caspi is at the National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. rcaspi@helix.nih.gov,

    Rachel R. Caspi

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DATABASES

OMIM

Graves' disease

multiple sclerosis

myasthenia gravis

pemphigus vulgaris

type 1 diabetes

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Glossary

Altered peptide ligand

(APL). A peptide analogue in which the key T-cell receptor contact residues are altered, leading to the induction of only a partial response by the T cells that are specific for the original agonist peptide. Some APLs may stimulate regulatory T cells without activating effector T cells.

Crohn's disease

A form of chronic inflammatory bowel disease that can affect the entire gastrointestinal tract, but is most common in the colon and terminal ileum. It is characterized by transmural inflammation, narrowing of the gut lumen and granuloma formation, and is thought to result from an abnormal T-cell-mediated immune response to commensal bacteria.

Epitope spreading

The de novo activation of autoreactive T cells by self antigens that have been released after B- or T-cell-mediated bystander damage.

Psoriasis

A chronic skin disease that affects 1–2% of the population, in which the skin becomes inflamed, producing red, thickened areas with silvery scales, most often on the scalp, elbows, knees and lower back. Recent evidence points to a T-cell-mediated pathogenesis in genetically susceptible individuals, which results in inflammation and epidermal hyperplasia.

Spondyloarthropathy

A group of inflammatory joint diseases that are associated with the MHC class I molecule HLA-B27. It is often associated with anterior uveitis.

Sympathetic ophthalmia

Destructive uveitis in one eye (sympathizing) following a penetrating wound to the other. It is considered to be an autoimmune response to antigens that are released from the wounded eye.

Vitiligo

A depigmenting disorder of the skin and hair that is caused by the destruction of melanocytes that produce cutaneous pigments.

Vogt–Koyanagi–Harada disease

A serious and potentially blinding condition that also targets the melanin in the anterior and the posterior pole of the eye.

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Caspi, R. Immunotherapy of autoimmunity and cancer: the penalty for success. Nat Rev Immunol 8, 970–976 (2008). https://doi.org/10.1038/nri2438

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