Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in metastatic melanoma. The Ig-CDR-based peptide C36L1 is able to restore macrophages and dendritic cells’ immunogenic functions and to inhibit metastatic growth in vivo. Mechanistically, we found that C36L1 interferes with the MIF-CD74 tumour-innate immune cells immunosuppressive signalling pathway and thereby restores an effective anti-tumour immune response. C36L1 directly binds to CD74 on macrophages and dendritic cells, disturbing CD74 structural dynamics and inhibiting MIF signalling through CD74. Our findings suggest that interfering with MIF-CD74 immunosuppressive signalling in macrophages and dendritic cells using peptide-based immunotherapy can restore the anti-tumour immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the anti-tumour immune response.

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Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽

10.3390/cancers12082226 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2226

Author(s):

Israa Shihab ◽

Bariaa A. Khalil ◽

Noha Mousaad Elemam ◽

Ibrahim Y. Hachim ◽

Mahmood Yaseen Hachim ◽

...

Keyword(s):

Breast Cancer ◽

Immune System ◽

Tumor Microenvironment ◽

Nk Cells ◽

Immune Cells ◽

Innate Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Cells ◽

Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

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The Role of Syk/CARD9-Coupled C-Type Lectin Receptors in Immunity toMycobacterium tuberculosisInfections

Clinical and Developmental Immunology ◽

10.1155/2010/567571 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Mohlopheni Jackson Marakalala ◽

Lisa M. Graham ◽

Gordon D. Brown

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Mycobacterium Tuberculosis ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Lectin Receptors ◽

Molecular Patterns

There is increasing interest in understanding the mechanisms underlying the interactions that occur betweenMycobacterium tuberculosisand host innate immune cells. These cells express pattern recognition receptors (PRRs) which recognise mycobacterial pathogen-associated molecular patterns (PAMPs) and which can influence the host immune response to the infection. Although many of the PRRs appear to be redundant in the control ofM. tuberculosisinfectionin vivo, recent discoveries have revealed a key, nonredundant, role of the Syk/CARD9 signalling pathway in antimycobacterial immunity. Here we review these discoveries, as well as recent data investigating the role of the Syk/CARD9-coupled PRRs that have been implicated in mycobacterial recognition, including Dectin-1 and Mincle.

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Special Issue: “Unraveling the Involvement of Adipose Tissue in Breast Cancer Progression”

International Journal of Molecular Sciences ◽

10.3390/ijms22105107 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5107

Author(s):

Tiziana Triulzi

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Cancer Progression ◽

White Adipose Tissue ◽

Immune Cells ◽

Breast Cancer Progression ◽

Cell Populations ◽

Special Issue ◽

Adipocyte Cell ◽

Heterogeneous Tissue

White adipose tissue (WAT) is a heterogeneous tissue that is composed of adipocytes and several non-adipocyte cell populations, including adipose progenitors, fibroblasts, endothelial and infiltrating immune cells [...]

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Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics

mSystems ◽

10.1128/msystems.00306-21 ◽

2021 ◽

Author(s):

Orna Ernst ◽

Mohd M. Khan ◽

Benjamin L. Oyler ◽

Sung Hwan Yoon ◽

Jing Sun ◽

...

Keyword(s):

Immune Response ◽

Cell Surface ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Pathway Activation ◽

Specific Receptors ◽

Species Specific

Macrophages and monocytes are innate immune cells playing an important role in orchestrating the initial innate immune response to bacterial infection and the tissue damage. This response is facilitated by specific receptors on the cell surface and intracellularly.

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Latest Advances in Small Molecule TLR 7/8 Agonist Drug Research

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191009165418 ◽

2019 ◽

Vol 19 (24) ◽

pp. 2228-2238 ◽

Cited By ~ 5

Author(s):

David C. McGowan

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Small Molecule ◽

Immune Cells ◽

Drug Research ◽

Innate Immune ◽

Innate Immune Cells ◽

Small Molecule Activation ◽

Evolutionarily Conserved ◽

Recent Developments

Toll-like receptors (TLRs) 7 and 8 play an important role in the activation of innate immune cells in mammals. These evolutionarily conserved receptors serve as important sentinels in response to infection. Activation of TLRs 7 and 8 triggers induction of a Th1 type innate immune response. The emergence of new structural and small molecule information generated in the last decade has contributed enormously to our understanding of this highly sophisticated process of innate immunity signaling. This review will focus on recent developments in the small molecule activation of TLR 7 and 8.

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27-Hydroxycholesterol acts on myeloid immune cells to induce T cell dysfunction, promoting breast cancer progression

Cancer Letters ◽

10.1016/j.canlet.2020.08.020 ◽

2020 ◽

Vol 493 ◽

pp. 266-283 ◽

Cited By ~ 1

Author(s):

Liqian Ma ◽

Lawrence Wang ◽

Adam T. Nelson ◽

Chaeyeon Han ◽

Sisi He ◽

...

Keyword(s):

Breast Cancer ◽

T Cell ◽

Cancer Progression ◽

Immune Cells ◽

Breast Cancer Progression ◽

Cell Dysfunction ◽

T Cell Dysfunction

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A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice

Blood ◽

10.1182/blood-2012-08-449306 ◽

2013 ◽

Vol 122 (2) ◽

pp. 243-252 ◽

Cited By ~ 61

Author(s):

Erika Zonari ◽

Ferdinando Pucci ◽

Massimo Saini ◽

Roberta Mazzieri ◽

Letterio S. Politi ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Myeloid Cells ◽

Innate Immune ◽

Cancer Development ◽

Antitumoral Activity ◽

Innate Immune Cells ◽

Breast Cancer Development ◽

Key Points

Key Points miR-155 knockdown in myeloid cells accelerates spontaneous breast cancer development. miR-155 is required by TAMs for deploying antitumoral activity.

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