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Sci Transl Med. 2013 Feb 13;5(172):172ra20. doi: 10.1126/scitranslmed.3004888.

Mucosal imprinting of vaccine-induced CD8⁺ T cells is crucial to inhibit the growth of mucosal tumors.

Author information

1
INSERM U970 PARCC, 75015 Paris, France.
2
Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.
3
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou (HEGP), 75015 Paris, France.
4
Laboratoire de Pharmacologie Chimique et Génétique, UMR 8151 CNRS, 75270 Paris, France.
5
Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort 94700, France.
6
INSERM, CIC-BT-505, 75014 Paris, France.
7
AP-HP, Groupe Hospitalier Cochin Broca Hotel-Dieu, Centre d'investigation clinique de vaccinologie Cochin Pasteur, 75014 Paris, France.
8
Institut Curie, Centre de Recherche, Traffic, Signaling, and Delivery Laboratory, 75248 Paris Cedex 05, France.
9
UMR144 CNRS, 75005 Paris, France.
10
UMR 1161 Virologie Inra, Anses, ENVA, 7 avenue du Général de Gaulle, 94704 Maisons-Alfort, France.
11
UR892 INRA, 78350 Jouy-en-Josas, France.
12
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
13
Hopital Bichat, Service d'Anatomie Pathologique, 75018 Paris, France.
14
Institut Gustave Roussy, INSERM U1015, CIC-BT507, Faculté Paris Sud Université Paris XI, 94805 Paris, France.
#
Contributed equally

Erratum in

  • Sci Transl Med. 2013 Mar 27;5(178):178er2. Suleman, Muhammed [corrected to Suleman, Muhammad].

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.

Comment in

PMID:
23408053
PMCID:
PMC4086646
DOI:
10.1126/scitranslmed.3004888
[Indexed for MEDLINE]
Free PMC Article

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