Tumor Immunology - The Role of Tumor-Associated Macrophages - Research Paper Example

 Introduction Macrophages are white blood cells formed as a result of discrimination of monocytes. They are known as phagocytes and play an imperative role in non-specific as well as specific defense mechanisms. They are known to stimulate lymphocytes along with induction of other immune cells to act in response to the pathogen. They do play an imperative role in tumor progression and proliferation. The function of macrophages in tumor growth and expansion is complex and intricate. Macrophages are prominently present in the stroma and also play imperative role in various malignancies. Macrophages are multipurpose cells act in response to the stimulus in diverse tumors they release various macromolecules encompassing growth factors, cytokines, chemokines, and enzymes that potentially control tumor augmentation, tumor angiogenesis, tumor invasion, and tumor metastasis (Lewis, 2006). Tumor Associated Macrophages (TAM) act upon invasive area where TAMs sway cancer cell motility, they also act on stroma and perivascular areas where they encourage metastasis, and play imperative role in avascular and perinecrotic regions so that hypoxic TAMs accelerate angiogenesis (Lewis, 2006). The present article deals with the role of TAMs in promoting tumor induction and its role as anti-tumor agent and also the role of TAMs in malignancies. It is now established that tumor cells potentially block or elude the actions of TAMs at the site of tumor. Molecules derived from tumor cells also activate TAM elevate survival as well as proliferation of tumor cells. On the other hand, TAMs induce tumor angiogenesis through the production of mitogens, growth factors and enzymes (Bingle, 2002). Monocyte-macrophage lineage cells get polarized activated into M1 and M2 cells. M1 form of macrophage activation encompass IFN-γ based cytokines, GM-CSF (granulocyte-macrophage colony stimulating factor), LPS and TNF. They are distinguished by IL-12, IL-23(both high), IL-10 (low) and profuse quantity of reactive oxygen and nitrogen intermediary and inflammatory cytokines. Whereas M2 is a macrophage activation as a result of IL-4, IL13, IC (Immune complexes), IL-10 as well as glucocorticoid hormones. M2 are involved in Th2 response and perform immunoregulatory functions and plays role in tumor progression (Biswas, 2006) (Mantovani, 2008) TAMs are known to play a direct role in activating tumor-promoting genes (Chen et al, 2005). It is reported that COX-2 mRNA are induced by macrophages is regulated by binding of NF-κB to its consensus sequence present in the promoter area (Chang et al, 2004). Research also displays the triggering role of macrophages for p38 MAPK/NF-κB/COX-2 cascades in Basal Cell Carcinomas (Hung et al, 2004). Zymography reports reveal the fact that macrophage induce BCC cells to secrete MMP-9 and MMP-9 enzyme activity. These activities were obstructed by the inhibition of p38 MAPK/NF-κB/COX-2 cascades. thereby establishing the role of MMP-9 for enhanced invasion of macrophages. It was reported that overexpression of COX-2 induces the expression of angiogenic factors bFGF and VEGF-A which are responsible for TAM mediated angiogenesis of human BCC cells (Tjiu, 2008). It is now established that in gradually mounting solid tumors, TAMs re-plan themselves to induce suppression of host defence by releasing explicit cytokines, prostanoids and numerous humoral mediators. The reaction is chaotic, causing inhibition of effectual anti-cancer cell-mediated immune mechanisms. Simultaneously, TAMs display tumor growth promoting features. The abridgment interprets progressive tumor growth and tumor cell propagation. Through circulation TAMs recruit to the tumor site by means of tumor-derived agents such as chemokines this helps them to intermingle with tumor cells and restrict at low oxygen tension tumor-host tissue interface (Siveen, 2008). The tumor microenvironment, encompasses cytokines and hypoxia, these two serve as a regulatory factors for proliferation and establishment of TAMs. When TAMs are activated by tumor cells, they potentially alter the ECM and promote cancer cell invasion as well as proliferation. The existence of wide-ranging TAM penetration is linked with cancer metastasis and meagre prognosis in numeroous human carcinomas (Siveen, 2008). Tumour growth diminution by means of TAMs is arbitrated by non-specific anti-tumour cytotoxic methods or initiation of explicit cell lytic impacts (Grabbe, 1994; Blachere, 1997). TAMs on the contrary demonstrates tumour cell growth-promoting impacts by releasing cytokines and prostanoids (Sunderkotter, 1994). During the process of cancer progression, macrophages, dendritic and NK cells get fascinated towards the tumor site and set off the immune response in opposition to transformed cells. They stimulate and offer tumor antigens to T cells, they eventually destroy tumor cells. Nevertheless, tumor cells potentially overcome the host defense machinery, enabling TAMs to play role in tumor proliferation through the secretion of growth factors, and by acting upon endothelial cells (Lamagna, 2006). Conclusion It is established that metastasis of cancer cells is not solely synchronized by deregulation of genes responsible for metastasis promotion or suppression. Metastasis is promoted due to interface between cells of stroma and cancer cells. The stromal cells chiefly comprise of macrophages called tumor associated macrophages or TAMs. These TAMs are formed from peripheral blood monocytes engaged into the tumor. When triggered by cancer cells, TAMs liberate an enormous variety of growth factors, proteolytic enzymes, cytokines, and other inflammatory mediators, some of these serve as the potential contributor in cancer metastasis. There are numerous mechanisms adopted by TAMs that are responsible for promoting cancer metastasis. These encompass tumor angiogenesis, tumor growth and proliferation, tumor cell migration or relocation and invasion. A complex association between TAMs and cancer cells has been observed known as paracrine-signaling networks to stimulate each other. TAMs-derived proteases, for instance matrix metalloproteinase, urokinase-type plasminogen activator, and cathepsin B are capable of promoting cancer cells metastasis. On the other hand TAMs play an imperative role in anti-tumor activity and therefore role of TAMs in promoting tumor or eliminating tumor is emerging as imperative study for cancer therapy. TAMs enhances the invasion and angiogenesis of human BCC. 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