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CD4+ T cell help in cancer immunology and immunotherapy

Nature Reviews Immunology (2018) | Download Citation


Cancer immunotherapy aims to promote the activity of cytotoxic T lymphocytes (CTLs) within a tumour, assist the priming of tumour-specific CTLs in lymphoid organs and establish efficient and durable antitumour immunity. During priming, help signals are relayed from CD4+ T cells to CD8+ T cells by specific dendritic cells to optimize the magnitude and quality of the CTL response. In this Review, we highlight the cellular dynamics and membrane receptors that mediate CD4+ T cell help and the molecular mechanisms of the enhanced antitumour activity of CTLs. We outline how deficient CD4+ T cell help reduces the response of CTLs and how maximizing CD4+ T cell help can improve outcomes in cancer immunotherapy strategies.

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J.B. received funding from the KWF Kankerbestrijding (Dutch Cancer Society; grant 11097).

Reviewer information

Nature Reviews Immunology thanks S. Mueller and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information


  1. Division of Tumour Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands

    • Jannie Borst
    • , Tomasz Ahrends
    •  & Nikolina Bąbała
  2. Leiden University Medical Center and ISA Pharmaceuticals, Leiden, Netherlands

    • Cornelis J. M. Melief
  3. Institute for Systems Immunology, Würzburg, Germany

    • Wolfgang Kastenmüller


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All authors contributed to researching data for the article, discussion of content and reviewing and editing of the manuscript before submission. J.B. and W.K. wrote the article.

Competing interests

J.B. is an inventor on a patent for CD27 agonist antibodies. C.J.M.M. is beneficiary of a management participation plan in ISA Pharmaceuticals, Leiden, Netherlands, is a named inventor on a patent for the use of synthetic long peptides as vaccines and is employed as Chief Scientific Officer by ISA Pharmaceuticals, which exploits this patent. The other authors declare no competing interests.

Corresponding author

Correspondence to Jannie Borst.


Effector functions

T cell functions that are required to eliminate infected cells or tumour cells, including the ability to infiltrate tissues and to produce specific cytokines, chemokines and cytotoxic molecules.

Memory functions

Functions that allow a previously activated T cell to maintain longevity and to more rapidly and effectively proliferate and exert effector functions after a second exposure to their cognate antigen.

Co-stimulatory signals

Signals in T cells that are induced upon initial, activating T cell receptor–CD3 support; these signals activate additional, so-called co-stimulatory signalling pathways, leading to proliferation, differentiation and survival of the T cells.

Antigen cross-presentation

The presentation of peptides derived from extracellular sources by antigen-presenting cells via MHC class I molecules.


A dysfunctional state characterized by impaired cytotoxicity and cytokine production in effector T cells.

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