{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:12:45Z","timestamp":1788667965573,"version":"build-2803163510"},"reference-count":25,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"AL Wealth Partners","award":["E558-00-0713-01"],"award-info":[{"award-number":["E558-00-0713-01"]}]},{"name":"NUS Healthy Longevity Translational Research Program","award":["HLTRP\/2022\/PS-03"],"award-info":[{"award-number":["HLTRP\/2022\/PS-03"]}]},{"name":"NIH\/NCI","award":["R21 CA140916"],"award-info":[{"award-number":["R21 CA140916"]}]},{"name":"NIH\/NIA","award":["P01 AG01751"],"award-info":[{"award-number":["P01 AG01751"]}]},{"name":"NIH\/NIA","award":["P30 AG013280"],"award-info":[{"award-number":["P30 AG013280"]}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/OFLCG\/002-2018"],"award-info":[{"award-number":["NMRC\/OFLCG\/002-2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["OF-LCG-19May-0028"],"award-info":[{"award-number":["OF-LCG-19May-0028"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["OFLCG23May-0039"],"award-info":[{"award-number":["OFLCG23May-0039"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A*STAR GAP Funding","award":["I23D1AG121"],"award-info":[{"award-number":["I23D1AG121"]}]},{"name":"A*STAR GAP Funding","award":["I24D1AG059"],"award-info":[{"award-number":["I24D1AG059"]}]},{"name":"A*STAR GAP Funding","award":["I24D1AG082"],"award-info":[{"award-number":["I24D1AG082"]}]},{"name":"Industry Alignment Fund-Industry Collaboration Fund","award":["I2001E0065"],"award-info":[{"award-number":["I2001E0065"]}]},{"name":"Industry Alignment Fund-Industry Collaboration Fund","award":["I2201E0014"],"award-info":[{"award-number":["I2201E0014"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tumour-associated macrophages (TAMs) are highly plastic immune cells that polarize into tumour killing M1-like or tumour promoting M2-like macrophages depending on signals in the tumour microenvironment (TME). Exercise training may induce TAMs towards M1-like phenotypes to slow cancer progression and metastasis. In this study, we explored the effects of wheel running in tumour-challenged mice by analysing immune cell expression in metastatic tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Archival breast cancer lung metastases tissues of old BALB\/c mice were subjected to multiplex immunofluorescence (mIHC) to quantify immune cell subsets. The immune cell expressions were then analysed against the primary mammary tumour mass, metastatic lung tissue area, as well as distance ran before and after tumour implant for the exercise mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Based on the mIHC results from control (n=9) and exercise (n=10) mice tissues, wheel running did not significantly alter immune cell expressions relative to lung metastases or mammary tumour. Correlations between immune cell expression and the metastatic foci area revealed significant trends. Of note, F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      CD163\n                      <jats:sup>+<\/jats:sup>\n                      or M2-like macrophage expression is positively correlated for both control (r=0.835,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.005) and exercise (r=0.669,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.034). The F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      cells or overall macrophage expression was only positively correlated in the control (r=0.764,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.017) group. Likewise, the mammary tumour mass was positively correlated in the control group (r=0.834,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.010) but not in the exercise group. Interestingly, F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      CD86\n                      <jats:sup>+<\/jats:sup>\n                      or M1-like macrophage cells (r=0.758,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.011) and M1\/M2 ratio (r=0.642,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.045) were only significantly correlated with mean distances ran after tumour implant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Voluntary wheel running may shift the expression of metastatic TAMs towards anti-tumour M1-like macrophages in a dose-dependent manner after tumour challenge. This study demonstrates the importance and potential of implementing exercise training in combination with immunotherapy to treat metastatic breast cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10732748261448644","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:35:26Z","timestamp":1788507326000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Voluntary Wheel Running Modulates Tumour-Associated Macrophage Polarization in Breast Cancer Lung Metastases of Old BALB\/C Mice, in a Dose-dependent Manner"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1824-7041","authenticated-orcid":false,"given":"Patrick Henry Sebastian","family":"Sitjar","sequence":"first","affiliation":[{"name":"National University of Singapore (NUS)"},{"name":"National University of Singapore (NUS)"},{"name":"National University Health System (NUHS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Yen","family":"Chong","sequence":"additional","affiliation":[{"name":"Technology and Research (A*STAR)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Ladiges","sequence":"additional","affiliation":[{"name":"University of Washington (UW)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe Poh Sheng","family":"Yeong","sequence":"additional","affiliation":[{"name":"Technology and Research (A*STAR)"},{"name":"Singapore General Hospital"},{"name":"Singapore General Hospital"},{"name":"Duke-National University of Singapore (NUS) Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6250-8251","authenticated-orcid":false,"given":"Jorming","family":"Goh","sequence":"additional","affiliation":[{"name":"National University of Singapore (NUS)"},{"name":"National University of Singapore (NUS)"},{"name":"National University Health System (NUHS)"},{"name":"National Cancer Centre Singapore (NCCS)"},{"name":"National University of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13171428"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1103149"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1295257"},{"key":"e_1_3_5_5_2","first-page":"158","article-title":"Exercise, physical activity and breast cancer: the role of tumor-associated macrophages","volume":"18","author":"Goh J","year":"2012","unstructured":"Goh J, Kirk EA, Lee SX, Ladiges WC. Exercise, physical activity and breast cancer: the role of tumor-associated macrophages. Exerc Immunol Rev. 2012;18:158-176.","journal-title":"Exerc Immunol Rev"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-018-0241-4"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.78"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010324"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.76136"},{"issue":"4","key":"e_1_3_5_10_2","first-page":"378","article-title":"Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent manner","volume":"4","author":"Goh J","year":"2014","unstructured":"Goh J, Endicott E, Ladiges WC. Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent manner. 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Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. 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