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en: Fibrocytes in tumor microenvironment: Identification of their fraction and novel therapeutic strategy

en: Fibrocytes were identified as bone marrow-derived myeloid cells that also have fibroblast-like phenotypes, such as ECM production and differentiation to myofibroblasts. Although fibrocytes are known to contribute to various types of tissue fibrosis, their functions in the tumor microenvironment are unclear. We focused on fibrocytes as pivotal regulators of tumor progression. Our previous studies have indicated that fibrocytes induce angiogenesis and cancer stem cell-like phenotypes by secreting various growth factors. In contrast, immune checkpoint inhibitor (ICI)-treated fibrocytes demonstrated antigen-presenting capacity and enhanced antitumor T cell proliferation. Taken together, these findings indicate that fibrocytes have multiple effects on tumor progression. However, the detailed phenotypes of fibrocytes have not been fully elucidated because the isolation of distinct fibrocyte clusters has not been achieved without culturing in ECM-coated conditions or intracellular staining of ECM. The development of single-cell analyses partially resolves these problems. Single-cell RNA sequences in CD45+ immune cells from tumor tissue identified ECM-expressing myeloid-like cells as distinct fibrocyte clusters. In addition, these findings enabled the isolation of tumor-infiltrating fibrocytes as CD45+CD34+ cells. These tumor-infiltrating fibrocytes demonstrated both antigen-presenting ability and differentiation into myofibroblast-like cancer-associated fibroblasts. Considering these functions of fibrocytes in tumor progression, molecular-targeting agents for the migration, activity, and differentiation of fibrocytes are promising therapeutic strategies. Furthermore, identification of specific cell surface markers and master regulators of fibrocytes will advance novel fibrocyte-targeting therapies. In this review, we discuss the multiple roles of tumor-infiltrating fibrocytes and novel cancer therapeutic strategies.

en: Cancer Science

ja: Cancer Science


en: 1細胞解析による腫瘍内fibrocyteの同定

ja: 1細胞解析による腫瘍内fibrocyteの同定

en: The Cell

ja: 細胞


en: 血管新生阻害剤に対する耐性獲得メカニズム

ja: 血管新生阻害剤に対する耐性獲得メカニズム

en: Experimental Medicine

ja: 実験医学


en: 免疫チェックポイント阻害薬の効果を増強する併用療法

ja: 免疫チェックポイント阻害薬の効果を増強する併用療法

en: Respiratory Molecular Medicine

ja: 分子呼吸器病