Abdel-Aziz A.K.Saadeldin M.K.D'Amico P.Orecchioni S.Bertolini F.Curigliano G.Minucci S.Department of Experimental OncologyIEOEuropean Institute of Oncology IRCCSMilanItaly; Department of Pharmacology and ToxicologyFaculty of PharmacyAin Shams UniversityCairoEgypt; Faculty of BiotechnologyOctober University for Modern Sciences and Arts6th October CityCairoEgypt; Division of Early Drug Development for Innovative TherapiesIEOEuropean Institute of Oncology IRCCSMilanItaly; Laboratory of Hematology-OncologyIEOEuropean Institute of Oncology IRCCSMilanItaly; Department of Oncology and Hemato-OncologyUniversity of MilanoMilanItaly; Department of BiosciencesUniversity of MilanMilanItaly2020-01-092020-01-0920199598049https://doi.org/10.1016/j.ejca.2019.08.013PubMedID31606656https://t.ly/0E76gScopusThe Food and Drug Administration has lately approved atezolizumab, anti-programmed death ligand 1 (PD-L1), to be used together with nanoparticle albumin-bound (nab) paclitaxel in treating patients with triple negative breast cancer (BC) expressing PD-L1. Nonetheless, immune checkpoint inhibitors (ICIs) are still challenged by the resistance and immune-related adverse effects evident in a considerable subset of treated patients without conclusive comprehension of the underlying molecular basis, biomarkers and tolerable therapeutic regimens capable of unleashing the anti-tumour immune responses. Stepping back to preclinical models is thus inevitable to address these inquiries. Herein, we comprehensively review diverse preclinical models of BC exploited in investigating ICIs underscoring their pros and cons as well as the learnt and awaited lessons to allow full exploitation of ICIs in BC therapy. 2019 Elsevier LtdEnglishBreast cancerCTLA-4Immune checkpoint inhibitorPD-1PD-L1Preclinical modelantineoplastic agentbiological markerimmune checkpoint inhibitorimmunological antineoplastic agentnicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitorunclassified drugadjuvant therapybreast cancercancer adjuvant therapycancer chemotherapycancer immunotherapycancer modelcancer resistancecancer transplantationcombination drug therapyex vivo studyexperimental designhumanimmune responsein vivo studymolecular biologymouse modelmurine modelmutational loadneoadjuvant therapynonhumanpractice guidelinepreclinical studypriority journalReviewtransgenic animaltumor immunitytumor vascularizationtumor volumeReviewhttps://doi.org/10.1016/j.ejca.2019.08.013PubMedID31606656