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Vaccines to treat cancer represent a new and promising avenue of therapy. The aim is to stimulate certain cells in the immune system, such as the T-CD8 lymphocytes, in order to cause the tumour to shrink. Many hopes are being pinned on these types of vaccines. Numerous trials are currently in progress, but some have suffered setbacks in the clinical phase even though they proved successful on animal models.  

So as to understand why this happens, Eric Tartour and his team (Université Paris Descartes, INSERM  Unit 970 PARCC, AP-HP) used mice to test the efficacy of two different routes of administration, the intramuscular route, on the one hand, and the intranasal route on the other. The tests were performed on a candidate vaccine against mucous, oropharyngeal cancers developed in collaboration with Ludger Johannes at the Institut Curie.

They proved that only vaccination via the mucosa will shrink a tumour in the lung or the ear, nose and throat (ENT) area. The same anti-cancer vaccine administered in the usual immunisation way, i.e., intramuscularly or subcutaneously, is ineffective.

“Our results may explain the failure of anti-tumoural vaccines designed to treat tumours of the mucosa in humans, and should lead to a change in how anti-cancer vaccines are used to target mucosal tumours”, explained Eric Tartour, Professor at Paris Descartes University and hospital doctor at the Hôpital Européen Georges Pompidou (AP-HP).

To try and explain the difference in efficacy, researchers sought to identify the mechanisms that operated differently depending on the method of administration. They showed that vaccination through the mucosa caused a certain protein (the mucous integrin CD49a) to be produced that enabled the T-CD8 lymphocytes (whose production is stimulated by the administration of the vaccine) to migrate into the tumour. Once they are at the site of the tumour, the T-CD8 lymphocytes destroy the cancerous cells.

In the opposite case, if this molecule is blocked it prevents the penetration of T lymphocytes into the mucosal tumour and prevents their anti-tumoural activity. The integrin CD49a is essential in the promotion of migration of the anti-tumoural lymphocytes produced through vaccination in the case of pulmonary tumours and ENT tumours and thus the efficacy of the vaccination in combatting mucosal cancers.

To check the applicability of these results in humans, the researchers analysed samples from patients suffering from lung cancer. Here again, they demonstrated the elevated expression of mucosal integrin CD49a on T-CD8 lymphocytes present in patients with lung tumours[1].

These results are encouraging for the future extrapolation of the study to humans.