Research ArticlesCancer Vaccine

Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors

Science Translational Medicine  13 Feb 2013:
Vol. 5, Issue 172, pp. 172ra20
DOI: 10.1126/scitranslmed.3004888

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The Nose Knows

“Life is a journey, not a destination.” (Ralph Waldo Emerson) And yet, in the most literal sense, life can depend on both the journey and the destination. The science behind cancer vaccination presupposes that if you can build a sufficient immune response against a tumor, the immune system can be used to attack cancer cells. But what if tumor-targeting cells can’t actually get to the tumor? Sandoval et al. now provide an answer to that question in the context of mucosal tumors.

There is a disconnect between successful vaccination of mucosal tumors in animal models and the failure of similar vaccinations in clinical trials. Sandoval et al. hypothesized that the preclinical model systems used—subcutaneous tumors—may provide a partial explanation. Systemically delivered (intramuscular) vaccines successfully inhibited subcutaneous tumors but not those found in the mucosa. The authors then overcame this difficulty by taking a page from infectious disease vaccinology—intranasal immunization. The same vaccine delivered to the mucosa induced tumor-specific CD8+ T cells that inhibited tumor growth in mucosal tumors. These CD8+ T cells expressed CD49a, which correlated to their homing to the mucosa. In this case, although the destination is critical, how you get there is equally important.