Tumor-Associated Macrophages

Tumor-associated macrophages (TAMs) are found in the tumor microenvironment (TME) of multiple cancer. They play a significant role in cancer cell development and survival. TAMs can reprogram the immunosuppressive microenvironment and promote tumor cell proliferation, invasion, and metastasis. It plays a dual role of “tumor promoter” and “ immune suppressor.” TAMs can promote tumor progression by producing mediators like IL-6, TNF-a, CCL2, CXCL8, and CXCL10, which are NF-KB mediated factors preventing apoptosis, creating tumor-supportive microenvironment. Additionally, they stimulate tumor angiogenesis and inhibit anti-tumor immune response mediated by the T cells. TAMs reduce the T cell & NK cell activity via expressing cell surface proteins or producing soluble factors like IDO, PD-L1, and TGF-B. It can also regulate Tregs to suppress T-cell activity indirectly.
Strategies regulating the signaling pathways that control the activation and function of TAMs can inhibit the growth and spread of cancer. Immune checkpoint inhibitors and monoclonal antibodies that target specific proteins expressed on the surface of TAMs.

Tumor-Associated Macrophages Antibody Panel

Biomarker VEGFA PDCD1LG2 NT5E FOLR2 CD80 CD163 CD14
Catalog-No. TA500289S

30 ul

VEGFA (VEGF) mouse monoclonal antibody, clone OTI4E3 (formerly 4E3)

TA808990S

30 ul

PDCD1LG2 mouse monoclonal antibody, clone OTI7B10 (formerly 7B10)

TA809085S

30 ul

NT5E mouse monoclonal antibody, clone OTI1G2 (formerly 1G2)

TA808026S

30 ul

FOLR2 mouse monoclonal antibody, clone OTI4G6 (formerly 4G6)

UM570055

30 ul

CD80 mouse monoclonal antibody, clone UMAB65

TA506380S

30 ul

CD163 mouse monoclonal antibody, clone OTI2G12 (formerly 2G12)

TA811528S

30 ul

CD14 mouse monoclonal antibody,clone OTI12C8

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Tumor Microenvironment(TME) and TAMs

The tumor microenvironment is a highly complex ecosystem with malignant cells, host immune cells (including macrophages, NK cells, polymorphonuclear cells, mast cells, dendritic cells, and T and B lymphocytes), and non-immune cells (endothelial cells, stromal cells) along with cancer-associated fibroblast and tumor-associated macrophages.
The tumor cells need oxygen and nutrients to support their high mitotic and metabolic rates, and a vasculature network is essential for its growth. Endothelial cells of the tumor promote hypoxic conditions, which is favorable for tumor growth as it leads to secreting proangiogenic factors ( like VEGF-B) and cause high interstitial fluid pressure creating a mechanical barrier for T-cell infiltration. The cancer-associated fibroblast participates in the arrangement of cells surrounding the tumor, creating a physical barrier for cytotoxic immune cell infiltration. Studies have shown the contribution of TAMs in immunosuppression in the TME, which is a significant cause of ineffective tumor immunotherapies.

Key biomarkers in TME being used for Tumor Immunotherapy

PD-1 PD-L1 CTLA4 TIM3 LAG-3 NR2F6 TIGIT VISTA BTLA

Types of TAM

Macrophages in the tumor microenvironment can be polarized into two functional states: M1 & M2 state. The M1 polarized macrophages, also known as the classically activated macrophages, respond to bacterial agents or IFN-Y. They produce proinflammatory and immunostimulatory cytokines like IL-6 and IL-23. Studies have shown that M1 macrophages have anti-tumoral properties; they scavenge and destroy phagocytosed tumor cells.

On the other hand, M2-polarized macrophages, also known as alternatively activated macrophages, have the function of tissue reconstruction, debris removal, and promoting angiogenesis. IL-4 and IL-13, and other factors activate M2 macrophages. Most tumor-associated macrophages resemble M2 macrophages, and some as M1. M1 & M2 macrophages are two faces of the same coin; their expression depends on the level of cytokines in the environment. This spectrum of M1 & M2 macrophages also changes during tumor development. Thus, understanding TAMs will help develop more effective immunotherapies.

Key macrophage biomarkers in tumor microenvironment

CD47 IDO Adenosine IL-41 TGF-B TLR STING CD40 CD39

Tumor-associated macrophages (TAMs) mediated immunosuppression

TAMs are a heterogeneous population of cells that display a range of phenotypes depending on the type of tumor and their microenvironment. TAMs use multiple mechanisms to inhibit anti-tumor immune response :

a) Production of inhibitory cytokines and chemokines: TAMs can secrete chemokines and cytokines that promote tumor development, such as IL-6, IL-8, and IL-10.

b) Amino-acid depletion - inhibits CD4 and CD8+ T cells by regulating L-tryptophan degradation in the Kynurenine pathway.

c) Inhibition of tumor cell phagocytosis- It regulates SIRPα/CD47 pathway to protect tumor cells from phagocytosis.

d) Production of PGE2 and Tregs-recruiting chemokine: It inhibits IFN-gamma production through regulating PGE2 production and upregulated Th17 response to inhibit T-cell response indirectly.

e) Direct engagement of T cell inhibitory receptor.