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Being intolerant of tumors

Toll ligands (black squares and triangles) augment antitumor vaccinations and increase survival. Pardoll/Macmillan

Using the immune system to attack cancers is a good idea, but it may only work if Toll-like receptors (TLRs) are activated to break tolerance, say Yiping Yang (Duke University, Durham, NC), Drew Pardoll (Johns Hopkins, Baltimore, MD), and colleagues.

The favored method for delivering cancer immunotherapy has been dendritic cells: they are the central antigen-presenting cells for generating T cell responses; they can be grown in vitro in large quantities; and their use in mice with cancer led to some spectacular results. "That led to a whole wave of excitement," says Pardoll. "But it hasn't really panned out."

Perhaps the biggest problem is tolerance. Most cancer immunotherapy focuses not on tumor-specific antigens, which vary too much because each tumor has different mutations, but on self-antigens that are overexpressed in the tumor. Although some collateral damage of normal self-tissue is alright for many tissues, the real problem is getting the immune response off the ground when it is challenged with a self-antigen.

Now Yang et al. show that viral but not dendritic cell vectors can do the job. Only the viral vectors can suppress tolerance to a cancer self-antigen in a mouse model, thus leading to increased survival. Ligands that activate TLRs also do the trick, and may be more promising in humans, as humans generally mount antibody responses that neutralize viral vectors.

Reference:

Yang, Y., et al. 2004. Nat. Immunol. 10.1038/ni1059.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 1420K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?