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Background <p>T-cell immunoglobulin and mucin domain containing protein 4 (TIM4), a phosphatidylserine receptor primarily expressed on antigen-presenting cells, has been implicated in phagocytosis and immune regulation in various diseases, including malignancies. 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.</p> Methods <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.</p> Results <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.</p> Conclusions <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.</p>

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Infiltration of TIM4-positive intratumoral macrophages serves as an adverse prognostic factor in breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Mio Yamaguchi-Tanaka,
  • Kiyoshi Takagi,
  • Miyu Takahashi,
  • Ai Sato,
  • Yuto Yamazaki,
  • Minoru Miyashita,
  • Takashi Suzuki

摘要

Background

T-cell immunoglobulin and mucin domain containing protein 4 (TIM4), a phosphatidylserine receptor primarily expressed on antigen-presenting cells, has been implicated in phagocytosis and immune regulation in various diseases, including malignancies. 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.

Methods

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.

Results

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.

Conclusions

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.