Being intolerant of tumors

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....