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We know that the immune system is a major barrier to the development of tumors, and so far, surgical treatment of cancer remains in many cases the gold standard for many solid tumors. However, the perioperative period is subject to many immunomodulations. Severa} perioperative factors such as surgical stress or inflammation contribute to this. The drugs of anesthesia would also participate in this immunomodulation. It appears that anesthesia techniques and the choice of drugs used during the perioperative period could affect the long-term outcome of cancer patients. The aim of this thesis is to focus on immunomodulations appearing during the perioperative period, more particularly those induced by certain anesthetic agents and to understand what the impacts on cancer recurrence are. Nous savons que le système immunitaire représente une barrière majeure à l'apparition de tumeurs, et de même que, à ce jour, le traitement chirurgical du cancer reste dans de nombreux cas le traitement de référence pour de nombreuses tumeurs solides. Cependant, la période périopératoire est sujette à de nombreuses immunomodulations. Plusieurs facteurs périopératoires tels que le stress chirurgical ou l'inflammation y contribuent. Les médicaments de l'anesthésie participeraient également à cette immunomodulation. Il apparait donc que les techniques d'anesthésies ainsi que le choix des drogues utilisées lors de la période périopératoire pourraient affecter le devenir à long terme des patients cancéreux. Le but de ce mémoire est de s'intéresser aux immunomodulations. Apparaissant au cours de la période périopératoire, plus particulièrement celles induites par certains agents anesthésiques et comprendre quels sont les impacts sur la récidive du cancer.

Immunomodulation --- Perioperative Period --- Antibodies, Neoplasm

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Medical research progresses are nowadays clearly linked to new technologies but also sometimes to revival of older molecules. Thalidomide is a good example in this matter. Today, this extremely toxic molecule, cause of a great tragedy in the 50ies (“thalidomide babies”), is used to treat life-threatening pathologies like cancer.
Ten years ago, cancer research enables the discovery of a new important property of thalidomide, namely, an anti-tumor activity through inhibition of angiogenesis.
The consecutive renewal of interest for this molecule led to the search for new derivatives endowed with a higher anticancer activity and a lesser toxicity than thalidomide. This resulted in a new class of drugs named Immunomodulatory drugs or ImiDs. Besides their antiangiogenic properties, these new molecules actually exert powerful immunomodulatory effects which prevent tumor growth. Today, different clinical studies support the great therapeutic potential of IMiDs in the treatment of multiple myeloma, a type of cancer characterized by plasmocytes proliferation A l’heure actuelle, la recherche scientifique ne cesse d’évoluer grâce aux nouvelles technologies toujours plus pointues mais aussi au renouveau de molécules anciennes. L’exemple de la thalidomide est à ce propos très illustratif. Ce médicament hautement tératogène, cause d’une grande tragédie dans les années 50 (« thalidomide babies ») est, en effet, aujourd’hui utilisé au service de pathologies lourdes comme le cancer.
Il y a une dizaine d’années, la recherche a permis la découverte d’une nouvelle propriété de la thalidomide, à savoir une action anticancéreuse par inhibition de l’angiogénèse.
Les chercheurs ont alors étudié plus largement ce médicament afin de développer de nouvelles molécules présentant une efficacité anti-tumorale accrue et une moindre toxicité. Ce travail a abouti au développement des Immunomodulatory drugs (IMiDs). Des effets immunomodulateurs puissants complètent l’activité anti-angiogénique de ces drogues. Différentes études cliniques attestent aujourd’hui de l’énorme potentiel des IMiDs dans le traitement du myélome multiple, une forme de cancer caractérisé par la prolifération des plasmocytes

Thalidomide --- Thalidomide --- Immunomodulation --- Multiple Myeloma --- lenalidomide --- pomalidomide

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

immunomodulation --- cancer --- inflammation --- kynurenine pathway --- tryptophan

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- immunomodulation --- cancer --- inflammation --- kynurenine pathway --- tryptophan --- immunomodulation --- cancer --- inflammation --- kynurenine pathway --- tryptophan

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Activation of innate immune system underlies both pathological and physiological inflammatory responses and is critical for the host. Regulated innate immune response is thus essential not only for the elimination of invading pathogens but also for the restoration of tissue homeostasis. The innate immune system relies on the expression of families of highly conserved Pattern Recognition Receptors (PRRs) by specialised immune cells such as macrophages or dendritic cells. Engagement of PRRs by microbial or host-derived danger signals coordinates the cellular innate immune response. While some receptors such as Toll-like Receptors (TLRs) and C-type Lectin Receptors (CLRs) are membrane bound, others like the Retinoic-acid-Inducible Gene I (RIG-I)-Like Receptors (RLRs), Nucleotide-binding Oligomerization Domain (NOD)-Like Receptors (NLRs) and several DNA receptors (e.g. AIM2, cGAS) are expressed in the cytosol. Moreover, several molecules released by innate immune cells including complement proteins and members of the pentraxin family act as soluble PRRs. Activation of PRRs initiate specific signal transduction cascades, which lead to transcription and secretion of inflammatory mediators, thereby facilitating inflammation. Furthermore, some PRRs can form large oligomeric protein complexes called inflammasomes that instigate proteolytic maturation of members of the IL-1 family of cytokines, thereby driving inflammatory programmed cell death. Current research on immunomodulation is focused on understanding the fundamental mechanisms that control the activation and regulation of innate immune cell function. This includes exciting advances in understanding signals that can polarize innate immune cells into different functional states, for instance from a more inflammatory to a more tolerogenic profile. However, this response of innate immune cells critically depends on several intrinsic and extrinsic factors such as their own biological status and their microenvironmental context, respectively. For instance, it is known that the extracellular matrix or biomaterials can modulate macrophage behavior and that autophagy flux is a critical regulator of inflammation. Consistent with this, there has been an increase in the development of novel drugs and biomaterials aimed at inducing immunomodulatory responses in targeted innate immune cell populations to be used in the context of tissue regeneration, cancer, autoimmune disease etc. Thus, a thorough understanding of immunomodulatory mechanisms of innate immune cells will guide the development of novel therapeutic strategies aimed to control inflammation-mediated pathologies. In this Research Topic, we aim to highlight recent advances in our understanding of the fundamental mechanisms controlling activation of innate immune cells and document new strategies to study and manipulate their immunomodulation.

Medicine --- Immunology --- innate immunity --- PRRs --- immunomodulation --- pattern recognition --- macrophage polarization