The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.
En 2019, les anticorps monoclonaux (Acm) vont représenter un marché mondial annuel de plus de cent milliards de dollars, soit près de 90 milliards d’euros. Outre leur utilisation en clinique, les anticorps monoclonaux sont utilisés également dans de nombreux tests diagnostiques et sont toujours des outils précieux pour la recherche fondamentale et appliquée. Quarante-quatre ans après la publication de Georges Köhler et César Milstein [1], des dizaines de congrès et séminaires de toute nature sur les anticorps monoclonaux se tiennent annuellement à travers le monde. Mais 44 ans plus tard, les travaux scientifiques qui ont amené à cette publication sont peu à peu oubliés et, dans bien des esprits, les anticorps monoclonaux ne sont qu’un business d’un multi-milliard euros/dollars comme un autre, déterminé par les marchés financiers et les résultats des derniers essais cliniques… Il est grand temps de rendre hommage à toute une génération de chercheurs fondamentalistes, à ces fous de science du xx e siècle, à ces chercheurs connus et souvent désormais méconnus, disséminés aux quatre coins du monde, qui ont exploré les frontières de l’inconnu d’alors et qui ont modelé et ciselé un savoir qui a débouché sur une technique d’obtention de molécules qui ont permis l’une des plus grandes révolutions thérapeutiques de ces vingt-cinq dernières années.
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