title: Tumour-associated macrophages as treatment targets in oncology.
abstract: Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin-yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.|Humanitas University, Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20133 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marchesi
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20133 Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Malesci
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Laghi
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.|Humanitas University, Via A. Manzoni 113, 20089 Rozzano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents