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However, even in the most favorable cases, half of these patients do not benefit from these therapies in the long term. It is hypothesized that the activation of host immunity by co\u2010delivering peptide antigens, adjuvants, and regulators of the transforming growth factor (TGF)\u2010\u03b2 expression using a polyoxazoline (POx)\u2010poly(lactic\u2010<jats:italic>co<\/jats:italic>\u2010glycolic) acid (PLGA) nanovaccine, while modulating the tumor\u2010associated macrophages (TAM) function within the tumor microenvironment (TME) and blocking the anti\u2010programmed cell death protein 1 (PD\u20101) can constitute an alternative approach for cancer immunotherapy. POx\u2010Mannose (Man) nanovaccines generate antigen\u2010specific T\u2010cell responses that control tumor growth to a higher extent than poly(ethylene glycol) (PEG)\u2010Man nanovaccines. This anti\u2010tumor effect induced by the POx\u2010Man nanovaccines is mediated by a CD8<jats:sup>+<\/jats:sup>\u2010T cell\u2010dependent mechanism, in contrast to the PEG\u2010Man nanovaccines. POx\u2010Man nanovaccine combines\u00a0with pexidartinib, a modulator of the TAM function, restricts the MC38\u00a0tumor growth, and synergizes with PD\u20101\u00a0blockade, controlling MC38\u00a0and CT26\u00a0tumor growth and survival. This data is further validated in the highly aggressive and poorly immunogenic B16F10\u00a0melanoma mouse model. Therefore, the synergistic anti\u2010tumor effect induced by the combination of nanovaccines with the inhibition of both TAM\u2010 and PD\u20101\u2010inducing immunosuppression, holds great potential for improving immunotherapy outcomes in solid cancer patients.<\/jats:p>","DOI":"10.1002\/advs.202300299","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T23:09:41Z","timestamp":1689116981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Polyoxazoline\u2010Based Nanovaccine Synergizes with Tumor\u2010Associated Macrophage Targeting and Anti\u2010PD\u20101 Immunotherapy against Solid Tumors"],"prefix":"10.1002","volume":"10","author":[{"given":"Ana I.","family":"Matos","sequence":"first","affiliation":[{"name":"Grouf of BioNanoSciences \u2010 Drug Delivery and Immunoengineering, Research Institute for Medicines (iMed.ULisboa), Department of Pharmacy, Pharmacology and Health Technologies Faculty of Pharmacy Universidade de Lisboa  Lisbon 1649\u2010003 Portugal"},{"name":"Faculdade de Medicina, Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Lisbon Academic Medical Center Universidade de Lisboa  Lisbon 1649\u2010028 Portugal"}]},{"given":"Carina","family":"Peres","sequence":"additional","affiliation":[{"name":"Grouf of BioNanoSciences \u2010 Drug Delivery and Immunoengineering, Research Institute for Medicines (iMed.ULisboa), Department of Pharmacy, Pharmacology and Health Technologies Faculty of Pharmacy Universidade de Lisboa  Lisbon 1649\u2010003 Portugal"},{"name":"Faculdade de Medicina, Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Lisbon Academic Medical Center Universidade de Lisboa  Lisbon 1649\u2010028 Portugal"}]},{"given":"Barbara","family":"Carreira","sequence":"additional","affiliation":[{"name":"Grouf of BioNanoSciences \u2010 Drug Delivery and Immunoengineering, Research Institute for Medicines (iMed.ULisboa), Department of Pharmacy, Pharmacology and Health Technologies Faculty of Pharmacy Universidade de Lisboa  Lisbon 1649\u2010003 Portugal"}]},{"given":"Liane I. 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