Mechanism for the recruitment of macrophages to cancer site. In vivo concentration gradient of monocyte chemotactic activity

Abstract

Background. Tumor stroma is characterized by the development of new blood vessels, a n inflammatory cell infiltration, and a fibrotic reaction. The inflammatory component of tumor stroma plays an important role in the modulation of tumor expansion. In this respect, macrophages constitute a major part of the inflammatory cell infiltration and can exert cytotoxic activity against tumor cells. The accumulation of macrophages in the vicinity of the tumor suggests their recruitment from circulating blood monocytes through the local release of chemotactic factors for monocytes. To detect the existence of a concentration gradient of monocyte chemotactic activity (MCA) between the tumor vicinity and blood vessels, malignant pleural effusions defined by the local presence of cancer cells were evaluated for quantification of MCA. Results. Unlike nonmalignant pleural effusions, malignant pleural effusions were characterized by the presence of increased levels of MCA, and in lung adenocarcinoma (a cancer with high inflammatory cell infiltration), pleural levels of MCA were significantly greater than in small cell lung carcinoma (a cancer with low inflammatory cell reaction). An MCA concentration gradient between pleural fluid and plasma was present in malignant effusions because pleural MCA levels in all cancer types were significantly greater than MCA levels in the plasma of the same patients. Thus, an increased local level of MCA is a feature of cancers with high inflammatory cell infiltration, and the presence of an in vivo concentration gradient of MCA suggests the direct role of this biologic activity in recruiting blood monocytes to the cancer site. Cancer 1992; 70:854-860. Methods. Conclusions.

MHC Class I-Related Neonatal Fc Receptor for IgG Is Functionally Expressed in Monocytes, Intestinal Macrophages, and Dendritic Cells

“…The interstitial pH within solid tumors has been observed to be below physiological levels, ranging from 5.6 -7.7, which includes the pH optimum of FcRn binding (50). Macrophages are recruited in the earliest phases of inflammation such as inflammatory bowel disease (52), and they are widely infiltrated in solid tumor tissues (53).…”

The ecology of brain tumors: lessons learned from neurofibromatosis-1

“…A dynamic relationship forms between the pre-neoplastic/ neoplastic and non-neoplastic stromal cell populations through stromagen and gliomagens release, which together facilitate tumorigenesis, tumor maintenance and glioma progression. endothelial growth factor (Forstreuter et al, 2002;Kerber et al, 2008), hepatocyte growth factor (Badie et al, 1999;Kunkel et al, 2001), monocyte chemoattractant protein-1 (Martinet et al, 1992;Leung et al, 1997) and the chemokine CX3CL1 (fractalkine) through activation of the CX3CR1 receptor (Held-Feindt et al, 2010). Monocyte chemoattractant protein-1 can also increase the surface expression of CX3CR1 on microglia (Green et al, 2006), thus providing amplification circuits for further microglia recruitment.…”

Differential effects of malignant mesothelioma cells on THP-1 monocytes and macrophages

“…M1 Mº are powerful immune effector cells characterized by a high ability to present antigens and to produce proinflammatory cytokines and toxic intermediates, while M2 Mº display a poor antigen-presenting capacity and are polarized to release many different immunosuppressive molecules as well as to promote angiogenesis and extracellular matrix degradation (6)(7)(8)(9). It has been indicated that TAMs, which derive almost entirely from circulating monocytes (Mo) recruited and differentiated in the tumor milieu (10)(11)(12), often display phenotypic features consistent with those of M2 Mº and, accordingly, can actively sustain tumor growth and contribute to generate an immunosuppressive microenvironment (7,13). Moreover, recent evidence demonstrated the existence of Mo with M2-like phenotypes, which could thus be a preferential source of M2 Mº and important players in tumor-induced immunosuppression (10,12 The definition of the role of individual immune cell types on the outcome of the anti-tumor immune responses is of pivotal importance for the rational design of new antineoplastic immunotherapy approaches.…”

“…It has been indicated that TAMs, which derive almost entirely from circulating monocytes (Mo) recruited and differentiated in the tumor milieu (10)(11)(12), often display phenotypic features consistent with those of M2 Mº and, accordingly, can actively sustain tumor growth and contribute to generate an immunosuppressive microenvironment (7,13). Moreover, recent evidence demonstrated the existence of Mo with M2-like phenotypes, which could thus be a preferential source of M2 Mº and important players in tumor-induced immunosuppression (10,12 The definition of the role of individual immune cell types on the outcome of the anti-tumor immune responses is of pivotal importance for the rational design of new antineoplastic immunotherapy approaches. In this respect, however, the functional role of the leukocytes infiltrating MM tissues is still poorly defined (4).…”