Tumor-induced immune dysfunction: the macrophage connection

Elgert, Klaus D.; Alleva, David G.; Mullins, David W.

doi:10.1002/jlb.64.3.275

Cited by 367 publications

(281 citation statements)

References 196 publications

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“…Unlike macrophages from healthy tissues, which are capable of presenting tumor-associated antigens, lysing tumor cells, and stimulating the antitumor functions of T cells and NK cells, TAMs in the tumor microenvironment lack these activities, leaving the host without the ability to mount an effective antitumor immune response. A number of studies have shown that tumor-derived molecules, like cytokines, growth factors, chemotactic molecules, and proteases, influence TAM functions (8,25,58). For example, tumor cells secrete IL-4, IL-6, IL-10, MDF, TGF-h1, and PGE 2 , which inhibit the cytotoxic activity of TAMs (8,58).…”

Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

“…A number of studies have shown that tumor-derived molecules, like cytokines, growth factors, chemotactic molecules, and proteases, influence TAM functions (8,25,58). For example, tumor cells secrete IL-4, IL-6, IL-10, MDF, TGF-h1, and PGE 2 , which inhibit the cytotoxic activity of TAMs (8,58). Moreover, TGF-h1, IL-10, and PGE 2 may suppress the expression of MHC class II molecules by macrophages in the tumor microenvironment as well as distant sites like the spleen and peritoneum.…”

Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

“…Moreover, TGF-h1, IL-10, and PGE 2 may suppress the expression of MHC class II molecules by macrophages in the tumor microenvironment as well as distant sites like the spleen and peritoneum. This effect may limit the ability of TAMs to present tumor-associated antigens to T cells effectively in these areas (8). Thus, tumors undergo immunoediting to down-regulate macrophage functions that are potentially dangerous to the tumor even in circumstances where recognizable tumor antigens are presented.…”

Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

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Distinct Role of Macrophages in Different Tumor Microenvironments

2006

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Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes. (Cancer Res 2006; 66(2): 605-12)

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Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

Section: Roles Of Tam In Tumor Progressionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct Role of Macrophages in Different Tumor Microenvironments

2006

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“…However, these cells are believed to have primarily a protumour function since both tumours and TAMs produce potent immunomodulating agents that suppress macrophage tumoricidal activity. Such tumour-produced molecules, including IL-4, IL-6, IL-10, CSF-1, TGFb and prostaglandin E2 (PGE2), and TAM-produced factors such as IL-10 and PGE2, contribute to the general immunosuppression of the host as well as the antitumour activity of macrophages (Elgert et al, 1998;Mytar et al, 2003). Although infiltration of macrophages is usually correlated with poor outcome (Hamada et al, 2002), recent studies have also shown that infiltrated macrophages may have an anti tumour action in colorectal cancer (Nakayama et al, 2002;Noguchi et al, 2003).…”

Section: Macrophagesmentioning

confidence: 99%

Role of infiltrated leucocytes in tumour growth and spread

2004

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Leucocytes are a major component of the tumour microenvironment. Recent studies have indicated that the infiltration and activity of these host cells are regulated by the tumour to promote its survival and progression. Through the production of an array of growth factors, proteases and angiogenic mediators, leucocytes in the tumour microenvironment promote tumour growth, angiogenesis and metastasis.

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“…M1 cells metabolize L-arginine mainly via inducible NO synthase (iNOS) 5 and thus produce NO. NO and its reactive intermediates contribute to M1-mediated tumoricidal and immune suppressive activities (26,47). In contrast, M2 cells are characterized by an alternative metabolic pathway for L-arginine, catalyzed by arginase, generating urea and polyamines.…”

Section: T He 1 Identification Of Tumor-associated Ags Has Providedmentioning

confidence: 99%

Nitric Oxide-Independent CTL Suppression during Tumor Progression: Association with Arginase-Producing (M2) Myeloid Cells

Liu

Ginderachter

Brys

et al. 2003

The Journal of Immunology

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Most of the mice bearing a s.c. BW-Sp3 lymphoma tumor mount a CD8+ T cell-mediated response resulting in tumor regression. Nonetheless, tumor progression occurs in some of the recipients and is associated with CTL inactivity. We demonstrated that T cell-activating APC were induced in regressors whereas T cell suppressive myeloid cells predominated in the spleen of progressors. Indeed, in vitro depletion of either the adherent or the CD11b+ populations restored T cell cytotoxicity and proliferation in these mice. This CTL inhibition was cell-to-cell contact-dependent but not mediated by NO. However, the same progressor suppressive cells prevented the activity of in vitro-restimulated CTLs derived from regressors in a cell-to-cell contact and NO-dependent fashion. Thus, either the NO-dependent or -independent suppressive pathway prevailed, depending on the target CTL population. In addition, the suppressive population expressed a high arginase activity, suggesting an association of the suppressive phenotype with alternatively activated (M2) myeloid cells. However, the high arginase activity is not directly involved in the suppressive process. Our results provide new insights for myeloid cell-mediated CTL inhibition during cancer progression.

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Tumor-induced immune dysfunction: the macrophage connection

Cited by 367 publications

References 196 publications

Distinct Role of Macrophages in Different Tumor Microenvironments

Distinct Role of Macrophages in Different Tumor Microenvironments

Role of infiltrated leucocytes in tumour growth and spread

Nitric Oxide-Independent CTL Suppression during Tumor Progression: Association with Arginase-Producing (M2) Myeloid Cells

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