{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T18:08:25Z","timestamp":1788718105684,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation","award":["451-03-137\/2025-03\/200111"],"award-info":[{"award-number":["451-03-137\/2025-03\/200111"]}]},{"name":"Medical Faculty of Military Medical Academy","award":["MF MMA 03\/22-24"],"award-info":[{"award-number":["MF MMA 03\/22-24"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite advances in immunotherapy, the treatment of breast cancer still remains a major global problem. In a previous study, we showed that co-blockade of Interleukin-33\/ST2 and Programmed death-1\/Programmed death-ligand (PD-1\/PD-L) signaling pathways strongly slows progression by enhancing the antitumor capacity of natural killer (NK) cells. The main aim of this study is to elucidate the exact effect of co-blockade on the T lymphocyte and macrophage effector cells. 4T1 cells were used to induct breast cancer in female BALB\/C and BALB\/C ST2\u2212\/\u2212 mice. The mice, both BALB\/C and BALB\/C ST2\u2212\/\u2212, were treated with anti-PD-1 antibody on certain days. After the mice were sacrificed, T cells and macrophages were analyzed using flow cytometry; dual co-blockade increased significantly the percentage of M1 macrophages in the tumor microenvironment, followed by an increase in expression of CD86+ and TNF\u03b1+. T cell accumulation was significantly higher in the spleen and within the tumor microenvironment, with elevation in activation markers such as Interleukin-17, CD69, NKG2D, and FasL and a decrease in Interleukin-10 and FoxP3 expression. Co-blockade of the PD-1\/PD-L axes and IL-33\/ST2 axes shows promising results in reestablishing an effective immune response and offers a new perspective on improving immune response to breast carcinoma.<\/jats:p>","DOI":"10.3390\/ijms26199600","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T12:22:03Z","timestamp":1759321323000},"page":"9600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Co-Targeting PD-1 and IL-33\/ST2 Pathways for Enhanced Acquired Anti-Tumor Immunity in Breast Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Marina Z.","family":"Jovanovi\u0107","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Otorhinolaryngology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Juri\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, Military Medical Academy, 11000 Belgrade, Serbia"},{"name":"Medical Faculty of the Military Medical Academy, University of Defense, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevena","family":"Gajovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1704-4208","authenticated-orcid":false,"given":"Miodrag","family":"Joci\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty of the Military Medical Academy, University of Defense, 11000 Belgrade, Serbia"},{"name":"Institute for Transfusiology and Haemobiology, Military Medical Academy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-6133","authenticated-orcid":false,"given":"Marina M.","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u0161ko","family":"Milev","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, Military Medical Academy, 11000 Belgrade, Serbia"},{"name":"Medical Faculty of the Military Medical Academy, University of Defense, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krstina Doklesti\u0107","family":"Vasiljev","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Emergency Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-2378","authenticated-orcid":false,"given":"Ivan","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Faculty of Medicine, University of East Sarajevo, 73300 Foca, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2147\/BCTT.S176070","article-title":"Epidemiological characteristics of and risk factors for breast cancer in the world","volume":"11","author":"Momenimovahed","year":"2019","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/1440-1681.12732","article-title":"Increased PD-L1 expression in breast and colon cancer stem cells","volume":"44","author":"Wu","year":"2017","journal-title":"Clin. 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