Tumor-derived interleukin-34 creates an immunosuppressive and chemoresistant tumor microenvironment by modulating myeloid-derived suppressor cells in triple-negative breast cancer

Kajihara, Nabeel; Kobayashi, Takuto; Otsuka, Ryo; Nio‐Kobayashi, Junko; Oshino, Tomohiro; Takahashi, Masato; Imanishi, Seiichi; Hashimoto, Ari; Wada, Haruka; Seino, K.

doi:10.1007/s00262-022-03293-3

Cited by 14 publications

(8 citation statements)

References 41 publications

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“…Circulating CD14 + HLA-DR lo/− monocytic MDSCs as an immune suppressive subset have potential clinical relevance for epithelial ovarian cancer progression [ 50 ] and HCC patients treated with trans-arterial radioembolization [ 65 ]. M-MDSCs are negatively associated with therapeutic response to immunotherapy, particularly CAR-T therapy [ 66 , 67 , 68 , 69 ], and with chemotherapy resistance [ 66 , 70 ].…”

Section: Monocytes and Monocyte-derived Cells In Tumorigenesismentioning

confidence: 99%

Monocytes in Tumorigenesis and Tumor Immunotherapy

Chen

Xia

et al. 2023

Cells

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Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, and new strategies for tumor biomarker identification and anti-tumor immunotherapy.

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Section: Monocytes and Monocyte-derived Cells In Tumorigenesismentioning

confidence: 99%

Monocytes in Tumorigenesis and Tumor Immunotherapy

Chen

Xia

et al. 2023

Cells

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Section: Impact Of Abnormal Breast Tumor Vascular On Immune Cellsmentioning

confidence: 99%

“…The immunosuppressive Tregs are recruited in the TME by the MDSCs that populate BCs [ 111 ]. Recently, it has been shown that BC cells release both IL-34, that induces myeloid stem cells’ differentiation into monocytic MDSCs [ 111 ], and CXCL17, that promotes the accumulation of MDSCs within the lung where they favor the development of a metastatic niche [ 112 ]. Results from further animal studies indicate that BC metastases to the lung are facilitated by the loss of the Shb gene in endothelial cells, which is followed by the recruitment of monocytic MDSCs in the lung [ 113 ].…”

Section: Impact Of Abnormal Breast Tumor Vascular On Immune Cellsmentioning

confidence: 99%

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Melaiu

Vanni

Portarena

et al. 2023

IJMS

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Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.

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“…Tumor-infiltrating Tregs are important factors in antitumor immunosuppression. Inducible interleukin-34 (IL-34) causes the conversion of bone marrow stem cells (BMSCs) into M-MDSCs, which indirectly attenuates the immune response by producing CCL22-recruiting Tregs in TME, causing chemoresistance (21). In addition, BC-induced MDSCs can induce effector T cells and convert them into Tregs through the IDO mechanism (52) have a retaliatory interaction, with MDSCs suppressing T cell activation while stimulated T cells mediating MDSC death via the Fas-FasL pathway (57).…”

Section: Immunosuppressive Effects Of Mdscsmentioning

confidence: 99%

“…In addition, various studies have been conducted to promote MDSCs differentiation in BC. Inhibiting the differentiation of M-MDSCs by utilizing ER inhibitors or anti-IL-34 monoclonal antibodies can suppress tumor growth by inhibiting M-MDSCs accumulation and restore tumor chemical sensitivity by promoting G-MDSCs accumulation (21). Svoronos N et al found that the Jak1/2 inhibitor Ruxolitinib significantly inhibited M-MDSCs differentiation and G-MDSCs expansion, and these inhibitory effects were significantly enhanced by concomitant use of the ERa antagonist methylpiperidino pyrazole (MPP) (127).…”

Section: Differentiation Of Mdscs To a Nonsuppressive Immune Statementioning

confidence: 99%

MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target

et al. 2023

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Women worldwide are more likely to develop breast cancer (BC) than any other type of cancer. The treatment of BC depends on the subtype and stage of the cancer, such as surgery, radiotherapy, chemotherapy, and immunotherapy. Although significant progress has been made in recent years, advanced or metastatic BC presents a poor prognosis, due to drug resistance and recurrences. During embryonic development, myeloid-derived suppressor cells (MDSCs) develop that suppress the immune system. By inhibiting anti-immune effects and promoting non-immune mechanisms such as tumor cell stemness, epithelial-mesenchymal transformation (EMT) and angiogenesis, MDSCs effectively promote tumor growth and metastasis. In various BC models, peripheral tissues, and tumor microenvironments (TME), MDSCs have been found to amplification. Clinical progression or poor prognosis are strongly associated with increased MDSCs. In this review, we describe the activation, recruitment, and differentiation of MDSCs production in BC, the involvement of MDSCs in BC progression, and the clinical characteristics of MDSCs as a potential BC therapy target.

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Tumor-derived interleukin-34 creates an immunosuppressive and chemoresistant tumor microenvironment by modulating myeloid-derived suppressor cells in triple-negative breast cancer

Cited by 14 publications

References 41 publications

Monocytes in Tumorigenesis and Tumor Immunotherapy

Monocytes in Tumorigenesis and Tumor Immunotherapy

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target

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