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

Sci Transl Med 13 February 2013:
Vol. 5, Issue 172, p. 172ra20
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004888

• Research Article

Cancer Vaccine

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

1. Federico Sandoval¹,²,
2. Magali Terme¹,²,*,
3. Mevyn Nizard¹,²,*,
4. Cécile Badoual¹,²,³,*,
5. Michel-Francis Bureau⁴,
6. Ludovic Freyburger⁵,
7. Olivier Clement¹,²,
8. Elie Marcheteau¹,²,⁶,⁷,
9. Alain Gey³,
10. Guillaume Fraisse¹,²,
11. Cécilia Bouguin¹,²,
12. Nathalie Merillon¹,²,
13. Estelle Dransart⁸,⁹,
14. Thi Tran¹,²,
15. Françoise Quintin-Colonna¹,²,⁵,
16. Gwennhael Autret¹,²,
17. Marine Thiebaud⁸,⁹,
18. Muhammed Suleman¹⁰,
19. Sabine Riffault¹¹,
20. Tzyy-Choou Wu¹²,
21. Odile Launay⁶,⁷,
22. Claire Danel¹³,
23. Julien Taieb¹,²,³,
24. Jennifer Richardson¹⁰,
25. Laurence Zitvogel¹⁴,
26. Wolf H. Fridman²,³,
27. Ludger Johannes⁸,⁹ and
28. Eric Tartour¹,²,³,⁶,†

+ Author Affiliations

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

+ Author Notes

• ↵* These authors contributed equally to this work.

1. ↵†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: F. Sandoval, M. Terme, M. Nizard, C. Badoual, M.-F. Bureau, L. Freyburger, O. Clement, E. Marcheteau, A. Gey, G. Fraisse, C. Bouguin, N. Merillon, E. Dransart, T. Tran, F. Quintin-Colonna, G. Autret, M. Thiebaud, M. Suleman, S. Riffault, T.-C. Wu, O. Launay, C. Danel, J. Taieb, J. Richardson, L. Zitvogel, W. H. Fridman, L. Johannes, E. Tartour, 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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