Sci Transl Med 13 February 2013:
Vol. 5, Issue 172, p. 172ra20
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004888
Vol. 5, Issue 172, p. 172ra20
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004888
- Research Article
Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors
- Federico Sandoval1,2,
- Magali Terme1,2,*,
- Mevyn Nizard1,2,*,
- Cécile Badoual1,2,3,*,
- Michel-Francis Bureau4,
- Ludovic Freyburger5,
- Olivier Clement1,2,
- Elie Marcheteau1,2,6,7,
- Alain Gey3,
- Guillaume Fraisse1,2,
- Cécilia Bouguin1,2,
- Nathalie Merillon1,2,
- Estelle Dransart8,9,
- Thi Tran1,2,
- Françoise Quintin-Colonna1,2,5,
- Gwennhael Autret1,2,
- Marine Thiebaud8,9,
- Muhammed Suleman10,
- Sabine Riffault11,
- Tzyy-Choou Wu12,
- Odile Launay6,7,
- Claire Danel13,
- Julien Taieb1,2,3,
- Jennifer Richardson10,
- Laurence Zitvogel14,
- Wolf H. Fridman2,3,
- Ludger Johannes8,9 and
- Eric Tartour1,2,3,6,†
+ Author Affiliations
- ↵†To whom correspondence should be addressed. E-mail: eric.tartour@egp.aphp.fr
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.
- Copyright © 2013, American Association for the Advancement of Science
Citation: Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors. Sci. Transl. Med. 5, 172ra20 (2013).
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