Science Translational Medicine
13 February 2013 vol 5, issue 172
http://stm.sciencemag.org/content/current

CANCER VACCINES
Vaccination Route Matters for Mucosal Tumors
Denise Nardelli-Haefliger, Jan C. Dudda, and Pedro Romero
13 February 2013: 172fs4

Abstract
Immunization route may be pivotal for tissue-specific localization of the effector T cell response (Sandoval et al., this issue).

Research Articles
Cancer Vaccine
Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors
Federico Sandoval, Magali Terme, Mevyn Nizard, Cécile Badoual, Michel-Francis Bureau, Ludovic Freyburger, Olivier Clement, Elie Marcheteau, Alain Gey, Guillaume Fraisse, Cécilia Bouguin, Nathalie Merillon, Estelle Dransart, Thi Tran, Françoise Quintin-Colonna, Gwennhael Autret, Marine Thiebaud, Muhammed Suleman, Sabine Riffault, Tzyy-Choou Wu, Odile Launay, Claire Danel, Julien Taieb, Jennifer Richardson, Laurence Zitvogel, Wolf H. Fridman, Ludger Johannes, and Eric Tartour
13 February 2013: 172ra20

Abstract
Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8+ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8+ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8+ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors.