title: Hormones and immunity in cancer: are thyroid hormones endocrine players in the microglia/glioma cross-talk?
abstract: Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3',5'-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments.
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Perrotta
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: De Palma
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy ; Scientific Institute IRCCS Eugenio Medea Bosisio Parini, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy ; Department for Innovation in Biological, Agro-food and Forest Systems (DIBAF), Università della Tuscia, Largo dell'Università snc Viterbo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Cervia
keywords: glioma; hypothyroidism; macrophages; microglia; thyroid hormones; tumor growth; tumor microenvironment