Factor chemotactic for mononuclear phagocytes was found in supernatant fluids of cultured human and mouse tumor cells. In 11 mouse tumors there was a correlation observed between chemotactic activity and macrophage content of neoplastic tissues. Tumor-derived chemoattractants appear to participate in the regulation of tumor-associated macrophages.
"In a tumor microenvironment, the TAMs have originated from the monocyte lineage by the factors that have expressed by stromal cells and the neoplastic cells. The chemokine CCL2 is the most important among these, as it has previously referred to as tumor derived chemotactic factor . Other Various factors like fibronectin, fibrinogen, cleavage products of extracellular matrix proteins, a variety of chemokine and cytokines like VEGF, PDGF and M-CSF have also involved in the recruitment of monocytes . "
[Show abstract][Hide abstract] ABSTRACT: The macrophages role within the tumor microenvironment has amended by a variety of factors, thus serves a vital role in tissue morphogenesis. The role of macrophages in health and disease differs enormously as the macrophage has shown dual functions. Macrophage has a basic role in antigen presentation serving as the first line of defense in diseases. However the presence of cytokines and growth factors, both together have regulated the macrophage to become negative effectors promoting tumor activity. Hence macrophages are a double edged weapon, and any imbalance in the regulatory mechanisms caused a shift from tumoricidal to tumorigenic activities. TAMs would be the main reason of the invasion in tumor microenvironment enhancing as well as tumor invasion, angiogenesis and metastasis promoting tumor genesis. Macrophages are the multifunctional cells which have conducted by the tumor cells to produce tumor promoting factors that enable the stimulation of angiogenesis, and tumor cell invasion. This fact has resulted initiation or promotion of tumor genesis, where the tumor has progressed to an upper malignant stage. The present review has focused on the tumor associated macrophages and their roles in tumor genesis.
Iranian Journal of Cancer Prevention 03/2014; 7(1):1-8.
"The infiltration of circulating lymphocytes to the tumour is facilitated by these chemokines. For example, breast, cervix and pancreatic tumours as well as ovarian tumour produce CC and CXC chemokines that are important mediators of macrophage and lymphocyte infiltration in those tumours272829. Interestingly, both Vδ1 and Vγ9δ2 T cells display distinct chemokine receptors that bestow these cells the property to migrate to the tumour site. "
[Show abstract][Hide abstract] ABSTRACT: γδ T lymphocytes represent a minor subset of peripheral blood in humans (<10%). γδ T cells expressing Vγ9Vδ2 T cell receptor recognise the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in cancer cells as a result of dysregulated mevalonate pathway. Aminobisphosphonates increase the endogenous pool of IPP in cells by blocking the enzyme farnesyl pyrophosphate synthase (FPPS) of the mevalonate pathway. Activated γδ T cells release copious amounts of interferon (IFN)-γ and tumour necrosis factor (TNF)-α and exhibit potent anti-tumour activity. Combination of γδ T cells with therapeutic monoclonal antibodies can efficiently mediate antibody dependent cellular cytotoxicity against tumours. These features makes γδ T cells attractive mediator of cancer immunotherapy. We review here, the basic properties and importance of γδ T cells in tumour immunity, and highlight the key advances in anti-tumour effector functions of γδ T cells achieved over the last few years and also summarize the results of the clinical trials that have been done till date. Future immunotherapeutic approach utilizing γδ T cells holds considerable promise for treatment of different types of cancer.
The Indian Journal of Medical Research 11/2013; 138(5):755-61. · 1.40 Impact Factor
"These immunosuppressive type 2 macrophages (M2) are marked by the expression of CD163 (the scavenger receptor) and CD206 (the mannose receptor), as well as traditional monocyte markers such as CD14, HLA-DR, and CD11b (Mantovani et al., 2002; Biswas and Mantovani, 2010). The tumor microenvironment promotes the generation of type 2 macrophages, as tumor cells can secrete factors (such as CCL-2) that recruit macrophages to the site of the tumor, and once there the immunosuppressive tumor microenvironment is able to drive these macrophage toward a type 2 phenotype (Bottazzi et al., 1983; Heusinkveld and van der Burg, 2011). These TAM are then able to contribute to the suppressive tumor microenvironment, expressing high levels of suppressive cytokines (such as TGF-β and IL-10), promoting tumor angiogenesis, and inhibiting anti-tumor immunity (Vasiljeva et al., 2006; Coffelt et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: While immune monitoring of tumor immunotherapy often focuses on the generation of productive Th1-type inflammatory immune responses, the importance of regulatory immune responses is often overlooked, despite the well-documented effects of regulatory immune responses in suppressing anti-tumor immunity. In a variety of malignancies, the frequency of regulatory cell populations has been shown to correlate with disease progression and a poor prognosis, further emphasizing the importance of characterizing the effects of immunotherapy on these populations. This review focuses on the role of suppressive immune populations (regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages) in inhibiting anti-tumor immunity, how these populations have been used in the immune monitoring of clinical trials, the prognostic value of these responses, and how the monitoring of these regulatory responses can be improved in the future.
Frontiers in Oncology 05/2013; 3:109. DOI:10.3389/fonc.2013.00109
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