Research ArticlesCancer Vaccines

Simultaneous Targeting of Toll- and Nod-Like Receptors Induces Effective Tumor-Specific Immune Responses

Science Translational Medicine  08 Feb 2012:
Vol. 4, Issue 120, pp. 120ra16
DOI: 10.1126/scitranslmed.3002868

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Whipping Tumors into Shape

Vaccines can tame even some of the most dreaded infections, priming the immune system to fight off the invading organism before you even know you’re sick. However, a successful vaccine against cancer has remained elusive. Tumors are wily—they can suppress or avoid the antitumor immune response. Now, in a mouse model, Garaude et al. have found a way to outfox these insidious cells by harnessing the immune system’s robust response to bacteria to bolster the fight against tumors.

Despite their diversity, different microbes have common needs, including replication, protection, and motility. The human immune system has evolved pattern recognition receptors to exploit these similarities—when they “see” a common bacterial feature, immune cells rapidly mount an inflammatory innate immune response, which then enhances the slower antigen-specific immune response. But can this innate immunity be co-opted to improve tumor vaccines?

Bacterial components have had some success as cancer vaccine adjuvants, but their use has introduced new hurdles as well. Garaude et al. devised a fresh strategy for adding a bacterial adjuvant to a cancer vaccine. The authors engineered tumor cells that produced the flagellin protein, which is a key component of the whiplike flagella that microbes use to move and which activates a type of pattern recognition receptors called Toll-like receptors (TLRs). When these cells were used to vaccinate mice, the flagellin not only activated TLR5 but also triggered another family of pattern recognition proteins—Nod-like receptors (NLRs). What’s more, these tumor cells induced an antigen-specific immune response in vivo, activating both cytotoxic and helper T cells and preventing tumor growth. By coordinately activating the TLR and NLR innate immune pathways, intracellular flagellin ensured that the immune response to tumor antigens was primed in an inflammatory context. Although they need to be repeated in humans, these studies suggest a new strategy for improving tumor vaccines to prevent cancer relapse.