title: Trial Watch-Small molecules targeting the immunological tumor microenvironment for cancer therapy.
abstract: Progressing malignancies establish robust immunosuppressive networks that operate both systemically and locally. In particular, as tumors escape immunosurveillance, they recruit increasing amounts of myeloid and lymphoid cells that exert pronounced immunosuppressive effects. These cells not only prevent the natural recognition of growing neoplasms by the immune system, but also inhibit anticancer immune responses elicited by chemo-, radio- and immuno therapeutic interventions. Throughout the past decade, multiple strategies have been devised to counteract the accumulation or activation of tumor-infiltrating immunosuppressive cells for therapeutic purposes. Here, we review recent preclinical and clinical advances on the use of small molecules that target the immunological tumor microenvironment for cancer therapy. These agents include inhibitors of indoleamine 2,3-dioxigenase 1 (IDO1), prostaglandin E2, and specific cytokine receptors, as well as modulators of intratumoral purinergic signaling and arginine metabolism.
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Aitziber
authors.initials: A
authors.lastname: Buqué
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Norma
authors.initials: N
authors.lastname: Bloy
authors.affiliation: Group of Immune receptors of the Innate and Adaptive System, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) , Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 13, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 13, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Wolf Hervé
authors.initials: WH
authors.lastname: Fridman
authors.affiliation: Sotio, Prague, Czech Republic; Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Fucikova
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
authors.affiliation: Sotio, Prague, Czech Republic; Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Spisek
authors.affiliation: Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; INSERM, U970, Paris, France; Paris-Cardiovascular Research Center (PARCC), Paris, France; Service d'Immunologie Biologique, Hôpital Européen Georges Pompidou (HEGP), AP-HP, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; INSERM, U1015, CICBT507, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France; Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
keywords: Adenosine; IDO1; PGE2; Tregs; myeloid-derived suppressor cells; tumor-associated macrophages