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However, the significance of TIM4 in the breast cancer microenvironment remains unclear. In this study, we investigated the localization and clinical significance of TIM4 in breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We immunolocalized TIM4 in human breast carcinoma tissues using immunohistochemistry (IHC) and multiplex fluorescence-immunohistochemistry (F-IHC) and examined its correlation with clinicopathological parameters and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TIM4 was highly expressed in both carcinoma cells and stromal cells in human breast carcinoma tissues. Multiplex F-IHC revealed that TIM4 was co-localized with CD68, a macrophage marker, whereas no co-localization was observed between TIM4 and CD80 (an M1 macrophage marker) or CD163 (an M2 macrophage marker). Prognostic analysis of 171 breast carcinoma tissues by IHC revealed that infiltration of TIM4-positive stromal cells was associated with an aggressive tumor phenotype, including increased proliferative and invasive potential, as well as poorer clinical outcomes. In contrast, TIM4 immunoreactivity in carcinoma cells showed no significant correlation with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that infiltration of TIM4-positive macrophages serves as a strong prognostic indicator in breast cancer and that TIM4 may represent a novel marker for tumor-promoting macrophages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12282-026-01825-8","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T12:27:05Z","timestamp":1768998425000},"page":"436-447","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Infiltration of TIM4-positive intratumoral macrophages serves as an adverse prognostic factor in breast cancer"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4276-5445","authenticated-orcid":false,"given":"Mio","family":"Yamaguchi-Tanaka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-6514","authenticated-orcid":false,"given":"Kiyoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyu","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuto","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Miyashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"1825_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Informed consent is not obtained because the design of the present study is a retrospective study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}