4.7 Review

The Innate Immune Microenvironment in Metastatic Breast Cancer

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Article Oncology

Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas

Funda Meric-Bernstam et al.

Summary: This study assessed the safety, pharmacokinetics, and efficacy of MIW815, a novel cyclic dinucleotide, in patients with advanced/metastatic cancers. Results showed that MIW815 was well tolerated, but had limited clinical activity as a single agent. However, evidence of systemic immune activation was observed.

CLINICAL CANCER RESEARCH (2022)

Review Immunology

GM-CSF: A Double-Edged Sword in Cancer Immunotherapy

Anil Kumar et al.

Summary: GM-CSF is a cytokine that drives the generation of myeloid cell subsets in response to stress, infections, and cancers. The levels of GM-CSF can either promote or inhibit cancer aggressiveness, depending on the specific conditions. The impact of GM-CSF signaling on cancer progression varies depending on the levels of GM-CSF, the cancer type, and the tumor microenvironment.

FRONTIERS IN IMMUNOLOGY (2022)

Review Oncology

The Prognostic and Clinical Value of Tumor-Associated Macrophages in Patients With Breast Cancer: A Systematic Review and Meta-Analysis

Changjun Wang et al.

Summary: This meta-analysis found that a high density of CD68+ and CD163+ tumor-associated macrophages (TAMs) is associated with poor overall survival and shorter disease-free survival in patients with breast cancer. Patients with high TAM density are more likely to have larger tumors, no vascular invasion, and positive estrogen receptor expression.

FRONTIERS IN ONCOLOGY (2022)

Review Oncology

Thromboembolism and Immune Checkpoint Blockade in Cancer Patients: An Old Foe for New Research

Mireille Langouo Fontsa et al.

Summary: Patients with cancer face an increased risk of venous and arterial thromboembolism, which is a major cause of death in these patients. In addition to individual patient risk factors, anticancer treatments can also increase the risk of thromboembolism. Immune checkpoint blockade, a commonly used treatment, has been associated with the occurrence of thromboembolic events.

TARGETED ONCOLOGY (2022)

Review Oncology

Targeting CTLA-4 in cancer: Is it the ideal companion for PD-1 blockade immunotherapy combinations?

Pushpamali De Silva et al.

Summary: Immunotherapy approaches targeting immune checkpoint molecules like CTLA-4 have revolutionized treatment of solid tumors and hematological malignancies by enhancing antitumor immune responses. However, the use of anti-CTLA-4 Abs may lead to autoimmune-like adverse events, though this higher incidence is associated with improved clinical benefit.

INTERNATIONAL JOURNAL OF CANCER (2021)

Article Multidisciplinary Sciences

Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung

Abhishek Tyagi et al.

Summary: Smoking has a profound impact on tumor immunity and tumor progression, with chronic nicotine exposure promoting the formation of a pre-metastatic niche in the lungs by recruiting pro-tumor N2-neutrophils that release lipocalin-2. Salidroside may be used to enhance the anti-tumor activity of neutrophils in breast cancer patients.

NATURE COMMUNICATIONS (2021)

Correction Multidisciplinary Sciences

Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy (vol 594, pg 566, 2021)

Ana Luisa Correia et al.

NATURE (2021)

Article Cell Biology

Monocytes secrete CXCL7 to promote breast cancer progression

Yi-Hsiang Wang et al.

Summary: This study identified an important immune cytokine, CXCL7, secreted by tumor infiltrating monocytes, to stimulate cancer cell migration, invasion, and metastasis, contributing to the promotion of breast cancer progression.

CELL DEATH & DISEASE (2021)

Review Oncology

The Crosstalk Between Tumor Cells and the Immune Microenvironment in Breast Cancer: Implications for Immunotherapy

Vincenzo Salemme et al.

Summary: The progression of breast cancer is influenced by genetic and epigenetic factors that involve interactions between tumor cells and the tumor microenvironment, particularly immune cells. Immune cells in the tumor microenvironment can have dual roles in cancer onset and progression, affecting both tumor suppression and promotion. Understanding the complex interplay between cancer and immune cells, as well as therapeutic strategies targeting this interaction, is crucial for developing effective combination treatments to overcome tumor immune evasion mechanisms and maximize the clinical benefits of current immunotherapies.

FRONTIERS IN ONCOLOGY (2021)

Meeting Abstract Oncology

Monalizumab and trastuzumab in metastatic HER2-positive breast cancer: MIMOSA-trial

V. C. M. Geurts et al.

ANNALS OF ONCOLOGY (2021)

Review Immunology

Targeting Innate Immunity in Breast Cancer Therapy: A Narrative Review

Yanqi Ye et al.

Summary: Immunotherapies show great potentials in improving breast cancer patient outcomes, with innate immunity playing a crucial role in eradicating tumors and controlling metastasis. Clinical trials focusing on innate immune pathways offer new hope for breast cancer therapies.

FRONTIERS IN IMMUNOLOGY (2021)

Review Endocrinology & Metabolism

Cross Talk Between Macrophages and Cancer Cells in the Bone Metastatic Environment

Lena Batoon et al.

Summary: The skeleton is a common site for cancer metastases due to the bone microenvironment providing conditions for cancer cell colonization. Tumor associated macrophages (TAMs) play a critical role in regulating tumorigenicity in multiple cancers, but their interactions with cancer cells in bone metastases are not fully understood. Studying these interactions may provide insights into the mechanisms of bone metastases and potential therapeutic targets for inhibiting disease progression.

FRONTIERS IN ENDOCRINOLOGY (2021)

Article Multidisciplinary Sciences

Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients

Marta Popeda et al.

Summary: Research shows that during lymphatic spread of luminal breast cancer, the local expression of complement system components decreases, and the reduction of tumoral complement C3 in lymph node metastases is associated with poor survival. This indicates a context-dependent role of complement C3 in breast cancer dissemination.

SCIENTIFIC REPORTS (2021)

Review Immunology

Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer

Anita K. Mehta et al.

Summary: Macrophages play a significant role in breast cancer progression, with their infiltration associated with poor prognosis. Tumor-associated macrophages impede productive tumor immunity by limiting antigen presentation and supporting tumor cell survival, angiogenesis, and metastasis, highlighting the urgent need to overcome their immune suppression for durable anti-tumor immunity in breast cancer.

FRONTIERS IN IMMUNOLOGY (2021)

Article Oncology

Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer

Xu Cao et al.

Summary: The study found that blocking CD47 and using cabazitaxel can significantly promote the programmed cell removal of TNBC cells, inhibiting tumor development and metastasis, providing a promising new strategy for TNBC treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

Article Biochemistry & Molecular Biology

Tumor infiltrating NK cell (TINK) subsets and functional molecules in patients with breast cancer

Somayeh Rezaeifard et al.

Summary: In this study, the frequency of NK cell subsets and functional molecules in breast tumor tissues of untreated patients was investigated using flow cytometry. The findings suggest that the accumulation of NK cells and the expression of activating NKG2D receptor by TINKs may play important roles in breast tumor regression, especially in patients without lymph node involvement. These observations may have implications for NK cell-based immunotherapy in cancer treatment.

MOLECULAR IMMUNOLOGY (2021)

Review Oncology

A review of immune checkpoint blockade in breast cancer

Benedetta Pellegrino et al.

Summary: The use of immune checkpoint blockers has shown potential in enhancing immune responses in breast cancer, particularly in the triple negative subtype and earlier lines of treatment. Some patients respond well to single agent ICB and achieve durable anti-metastatic effects.

SEMINARS IN ONCOLOGY (2021)

Article Biochemistry & Molecular Biology

Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer

Mayu Imamura et al.

Summary: The interaction between breast cancer cells and fibroblasts plays a minor role in the production of monocyte chemoattractant protein-1 (MCP-1). While cancer cells can communicate with fibroblasts through platelet-derived growth factors (PDGFs), this communication does not significantly impact MCP-1 production or cancer progression in this model. Understanding the complex crosstalk between cancer cells and stromal cells may help identify new targets for treating breast cancer patients.

CURRENT ISSUES IN MOLECULAR BIOLOGY (2021)

Article Medicine, Research & Experimental

Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer

Yiqing Tan et al.

Summary: This study identified the tumor suppression role of DRD2 in BrCa through downregulation due to promoter methylation, correlation with longer survival in HER2-positive patients, promotion of drug sensitivity, inhibition of tumorigenesis, induction of apoptosis and necroptosis, interaction with various genes to restrict signaling pathway activation, modulation of the microenvironment, and providing predictive and therapeutic targets for BrCa.

THERANOSTICS (2021)

Article Immunology

An Immunoregulatory Role for Complement Receptors in Murine Models of Breast Cancer

Fazrena Nadia Md Akhir et al.

Summary: The complement system plays a role in regulating tumor growth, with pharmacological targeting of C3aR and C5aR1 receptors showing protective effects in murine breast cancer models. The study found that while a C5aR1 antagonist had no effect on tumor growth, a dual C3aR/C5aR1 agonist significantly slowed mammary tumor progression. The low expression of C3aR and C5aR1 in mammary carcinoma cells suggests that the anti-tumor effects of the dual agonist may be indirect, possibly through immune response regulation.

ANTIBODIES (2021)

Review Pharmacology & Pharmacy

Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity

Yu Fu et al.

ACTA PHARMACEUTICA SINICA B (2020)

Article Medicine, Research & Experimental

Bone Tropism in Cancer Metastases

Hai Wang et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2020)

Review Oncology

Tumor-Associated Macrophages: Recent Insights and Therapies

Jiawei Zhou et al.

FRONTIERS IN ONCOLOGY (2020)

Article Immunology

Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth

Ruo-Yu Ma et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

Review Biochemistry & Molecular Biology

Overview of New Treatments with Immunotherapy for Breast Cancer and a Proposal of a Combination Therapy

Miguel Angel Galvan Morales et al.

MOLECULES (2020)

Article Multidisciplinary Sciences

Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+T cells

Clara Gomez-Aleza et al.

NATURE COMMUNICATIONS (2020)

Review Biochemistry & Molecular Biology

An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer

Dinh-Toi Chu et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Review Immunology

In vivo Differentiation of Human Monocytes

Alice Coillard et al.

FRONTIERS IN IMMUNOLOGY (2019)

Review Oncology

Role of the complement system in the tumor microenvironment

Ronghua Zhang et al.

CANCER CELL INTERNATIONAL (2019)

Review Oncology

Targeting PD-1 in cancer: Biological insights with a focus on breast cancer

Cinzia Solinas et al.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2019)

Review Medicine, Research & Experimental

The role of the complement system in cancer

Vahid Afshar-Kharghan

JOURNAL OF CLINICAL INVESTIGATION (2017)

Review Oncology

Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy

Michael A. Cannarile et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2017)

Article Immunology

Bench to bedside: NK cells and control of metastasis

Yelena Krasnova et al.

CLINICAL IMMUNOLOGY (2017)

Review Biochemistry & Molecular Biology

RANK-RANKL signalling in cancer

Nathalie Renema et al.

BIOSCIENCE REPORTS (2016)

Article Cell Biology

Macrophage Metabolism Controls Tumor Blood Vessel Morphogenesis and Metastasis

Mathias Wenes et al.

CELL METABOLISM (2016)

Article Multidisciplinary Sciences

Visualization of immediate immune responses to pioneer metastatic cells in the lung

Mark B. Headley et al.

NATURE (2016)

Review Immunology

Dendritic Cells and Cancer Immunity

Alycia Gardner et al.

TRENDS IN IMMUNOLOGY (2016)

Article Microbiology

Myeloid Cell Turnover and Clearance

William J. Janssen et al.

MICROBIOLOGY SPECTRUM (2016)

Article Microbiology

Myeloid Cell Origins, Differentiation, and Clinical Implications

Kipp Weiskopf et al.

MICROBIOLOGY SPECTRUM (2016)

Review Oncology

Neutrophils in cancer: neutral no more

Seth B. Coffelt et al.

NATURE REVIEWS CANCER (2016)

Review Oncology

Neutrophils: important contributors to tumor progression and metastasis

Agnieszka Swierczak et al.

CANCER AND METASTASIS REVIEWS (2015)

Review Immunology

The interaction of anticancer therapies with tumor-associated macrophages

Alberto Mantovani et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2015)

Article Multidisciplinary Sciences

Tumour exosome integrins determine organotropic metastasis

Ayuko Hoshino et al.

NATURE (2015)

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The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

Thomas R. Cox et al.

NATURE (2015)

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Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils

Amy-Jo Casbon et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2015)

Meeting Abstract Oncology

Phase I study of RG7155, a novel anti-CSF1R antibody, in patients with advanced/metastatic solid tumors.

Carlos Alberto Gomez-Roca et al.

JOURNAL OF CLINICAL ONCOLOGY (2015)

Review Immunology

Origin and Functions of Tissue Macrophages

Slava Epelman et al.

IMMUNITY (2014)

Review Oncology

CSF-1R Signaling in Health and Disease: A Focus on the Mammary Gland

Amy Renee Sullivan et al.

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA (2014)

Review Oncology

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Solid Tumors: A Systematic Review and Meta-Analysis

Arnoud J. Templeton et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2014)

Review Biochemistry & Molecular Biology

Harnessing the immune system for the treatment of breast cancer

Xinguo Jiang

JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B (2014)

Article Oncology

VDR Status Arbitrates the Prometastatic Effects of Tumor-Associated Macrophages

Yan Zhang et al.

MOLECULAR CANCER RESEARCH (2014)

Article Oncology

STING Ligand c-di-GMP Improves Cancer Vaccination against Metastatic Breast Cancer

Dinesh Chandra et al.

CANCER IMMUNOLOGY RESEARCH (2014)

Article Oncology

Bimodal role of Kupffer cells during colorectal cancer liver metastasis

Shu Wen Wen et al.

CANCER BIOLOGY & THERAPY (2013)

Review Biochemistry & Molecular Biology

Microenvironmental regulation of tumor progression and metastasis

Daniela F. Quail et al.

NATURE MEDICINE (2013)

Review Oncology

Emerging targeted agents in metastatic breast cancer

Dimitrios Zardavas et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2013)

Review Biotechnology & Applied Microbiology

Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab

David L. Lacey et al.

NATURE REVIEWS DRUG DISCOVERY (2012)

Article Multidisciplinary Sciences

Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function

Yanyan Wang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

Review Cell Biology

Mesenchymal stem cells in tumor development Emerging roles and concepts

Benjamin G. Cuiffo et al.

CELL ADHESION & MIGRATION (2012)

Review Immunology

Coordinated regulation of myeloid cells by tumours

Dmitry I. Gabrilovich et al.

NATURE REVIEWS IMMUNOLOGY (2012)

Article Biochemistry & Molecular Biology

Hypoxia induces RANK and RANKL expression by activating HIF-1α in breast cancer cells

Zhen-Ning Tang et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2011)

Review Hematology

Mast cell modulation of the vascular and lymphatic endothelium

Christian A. Kunder et al.

Article Medicine, Research & Experimental

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

Brian D. Lehmann et al.

JOURNAL OF CLINICAL INVESTIGATION (2011)

Article Multidisciplinary Sciences

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Bin-Zhi Qian et al.

NATURE (2011)

Review Biochemistry & Molecular Biology

Macrophage Diversity Enhances Tumor Progression and Metastasis

Bin-Zhi Qian et al.

Article Biotechnology & Applied Microbiology

Cabazitaxel

Matthew D. Galsky et al.

NATURE REVIEWS DRUG DISCOVERY (2010)

Article Multidisciplinary Sciences

Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes

Marcin Kowanetz et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Immunology

IL4Rα+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients

Susanna Mandruzzato et al.

JOURNAL OF IMMUNOLOGY (2009)

Article Hematology

Divergent effects of hypoxia on dendritic cell functions

Alessandra Mancino et al.

Article Biochemistry & Molecular Biology

Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells

Karin Loser et al.

NATURE MEDICINE (2006)

Review Oncology

Bone marrow cells in the 'pre-metastatic niche': within bone and beyond

Rosandra N. Kaplan et al.

CANCER AND METASTASIS REVIEWS (2006)

Review Oncology

Preparing the Soil: The premetastatic niche

Rosandra N. Kaplan et al.

CANCER RESEARCH (2006)