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Cancer immunotherapy – revisited

Nature Reviews Drug Discovery volume 10, pages 591–600 (2011)Cite this article

Subjects

Key Points

  • Clinical development of immunotherapy has been hampered by the complexity of defining the optimal dose and schedule, and the lack of financial support.

  • There is an urgent need for assays that can adequately monitor the induced antitumour immune response and predict the response to immunotherapy.

  • The kinetics of antitumour responses are considerably different between immunotherapy and cytotoxic chemotherapy, as initial progression and even the appearance of new lesions may precede tumour shrinkage following immunotherapy.

  • The clinical applicability of immunotherapy has recently been boosted by the positive results of various approaches, such as CTLA4-specific antibody therapy.

  • Recent findings on a positive interaction between immunotherapy and chemotherapy warrant further investigations

Abstract

Our insight into antitumour immune responses has increased considerably during the past decades, yet the development of immunotherapy as a treatment modality for cancer has been hampered by several factors. These include difficulties in the selection of the optimal dose and schedule, the methods of evaluation, and financial support. Although durable clinical remissions have been observed with various immunotherapeutic strategies, the percentage of patients who benefited from these interventions has remained too small to justify the general use of such strategies. However, the recent positive results of clinical trials with novel immunoactive drugs as well as the unexpected finding of a positive interaction between immunotherapy and chemotherapy may herald a new era for the immunotherapy of cancer.

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Figure 1: Examples of positive immunological effects of cytotoxic chemotherapeutics and targeted therapies.

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Acknowledgements

W.J.L. is supported by a Translation Research Fellowship of the Dutch Cancer Society and by the Netherlands Organization for Scientific Research (Grant 920-03-250).

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Authors and Affiliations

  1. Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen, 6500HB, The Netherlands

    W. Joost Lesterhuis & Cornelis J. A. Punt

  2. Divisions of Medical Oncology and Immunology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands

    John B. A. G. Haanen

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  1. W. Joost Lesterhuis
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  2. John B. A. G. Haanen
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  3. Cornelis J. A. Punt
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Correspondence to Cornelis J. A. Punt.

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Glossary

Cytotoxic T lymphocyte

Cytotoxic (CD8+) lymphocytes can kill tumour cells following recognition of tumour-associated antigens that are presented by major histocompatibility complex class I.

Cytotoxic T lymphocyte-associated antigen 4

(CTLA4). A co-inhibitory molecule that is expressed by T cells. Binding of its ligands B7.1 or B7.2 on antigen-presenting cells results in negative regulation of T cell activity.

Toll-like receptor 4

(TLR4). A member of the Toll-like receptor family of innate immune receptors that recognize molecular patterns of microbes or danger signals derived from tissue damage.

NLRP3

NOD-, LRR and pyrin domain-containing 3. This is a pyrin-like protein that is involved in inflammation and immune responses.

Crosspresentation

The mechanism by which certain APCs take up, process and present extracellular antigens on MHC class I molecules to stimulate cytotoxic T cells. This property is atypical, as most cells exclusively present peptides from endogenous proteins on MHC class I molecules.

Immunogenic cell death

The process of immunogenic cell death takes place when dying tumour cells provide an alerting or activating signal to the immune system.

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Lesterhuis, W., Haanen, J. & Punt, C. Cancer immunotherapy – revisited. Nat Rev Drug Discov 10, 591–600 (2011). https://doi.org/10.1038/nrd3500

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