De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent

Visser, Karin E. de; Korets, Lidiya; Coussens, Lisa M.

doi:10.1016/j.ccr.2005.04.014

Cited by 736 publications

(584 citation statements)

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“…Adoptive transfer of B lymphocytes or serum into B-cell-deficient/HPV16 mice restored innate immune cell infiltration into premalignant tissue and reinstated necessary parameters for full malignancy (e.g. chronic inflammation, angiogenic vasculature and hyperproliferative epidermis) [11]. These findings suggest a model in which B lymphocytes are crucial in establishing chronic inflammation associated with de novo carcinogenesis; however, as B cells do not infiltrate the precancerous tissues, it was suggested that infiltration and functions of innate immune cells must be orchestrated remotely [12], suggesting that lymphocyte-derived cytokines and/or antibodies may drive the cancer-promoting inflammation.…”

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confidence: 95%

“…A first original report on B cells and cancer progression, in a transgenic mouse model of inflammation-associated cancer (HPV16 mice), demonstrated the importance of B cells in de novo epithelial carcinogenesis [11]. Adoptive transfer of B lymphocytes or serum into B-cell-deficient/HPV16 mice restored innate immune cell infiltration into premalignant tissue and reinstated necessary parameters for full malignancy (e.g.…”

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Convergent pathways of macrophage polarization: The role of B cells

et al. 2010

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The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote infiltration of leukocyte populations, among which tumor-associated macrophages (TAM) represent a paradigm for cancer-promoting inflammation. TAM orchestrate various aspects of cancer, including diversion and skewing of adaptive responses, cell growth, angiogenesis, matrix deposition and remodelling, the construction of a metastatic niche and actual metastasis, response to hormones and chemotherapeutic agents. Several lines of evidence indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, suggesting that during tumor progression macrophages undergo a phenotypic ''switch'', eventually exhibiting the alternatively activated, ''M2'', phenotype that is associated with immunosuppression, promotion of tumor angiogenesis and metastasis. Although recent studies have attempted to address the role of microenvironmental signals on TAM ''reprogramming'', the interplay between innate and adaptive immunity is emerging as a crucial step of this event. In this issue of the European Journal of Immunology, a study demonstrates that B1 lymphocytes expressing IL-10 play a key role in promoting a pro-tumoral M2-biased phenotype of macrophages. This article defines a new in vivo pathway of macrophage polarization and suggests that targeting B cells is a possible therapeutic intervention to reinstate anticancer functions by TAM. Clinical and experimental evidence has highlighted that a major leukocyte population present in tumors, the so-called tumorassociated macrophages (TAM), is the principal component of the leukocyte infiltrate supporting tumor growth [1]. As macrophages represent a primary line of the innate or front-line defense mechanisms, this evidence has also underlined the ''immune paradox'' represented by TAM [2]. Over the past years, the mechanisms supporting the pro-tumoral functions of TAM have been increasingly clarified and in several experimental tumor models, the activation of an inflammatory response (most frequently mediated by macrophages) has been shown to play an essential role for full neoplastic transformation and progression. Recent reports have established that the acquisition of protumoral M2 functions by TAM is driven by various cytokines and signals expressed within the tumor microenvironment [3]. Among these, IL-10, PGE2, TGF-b and CSF-1 were reported to induce the M2-polarization of macrophages [3][4][5]. Based on the In a model of mammary carcinoma, myeloid-derived suppressor cells were shown to contribute to tumor progression by suppressing T-cell activation and inducing an M2-like phenotype of TAM, (increased IL-10 and decreased IL-12 production) [10].The role of B cells in solid tumor development is well characterized, for example B-cell-deficient mice (mMT) exhibited resistance to several type of syngeneic tumors, including EL4 lymphoma, MC38 colon carcinoma and B16 or D5 melanoma [9]. A first original report on B cells and can...

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Convergent pathways of macrophage polarization: The role of B cells

et al. 2010

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“…7 Progression of human papillomavirus type 16 E6/E7-driven squamous carcinogenesis in transgenic mice is significantly diminished in the absence of B cells. 8,9 In this preclinical tumor model, promotion of the early steps of carcinogenesis is achieved through deposition of IgG autoantibody in the neoplastic parenchyma and immune complex/FcgR ligation of mast cells and macrophages, eventually fostering proangiogenic and immunosuppressive gene expression programs. 8,9 Similarly, skin chemical carcinogenesis by two-stage application of the DNA damaging agent DMBA and the tumor promoter TPA occurs more rapidly in B-cell-proficient mice than in B-celldeficient mice.…”

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confidence: 99%

“…8,9 In this preclinical tumor model, promotion of the early steps of carcinogenesis is achieved through deposition of IgG autoantibody in the neoplastic parenchyma and immune complex/FcgR ligation of mast cells and macrophages, eventually fostering proangiogenic and immunosuppressive gene expression programs. 8,9 Similarly, skin chemical carcinogenesis by two-stage application of the DNA damaging agent DMBA and the tumor promoter TPA occurs more rapidly in B-cell-proficient mice than in B-celldeficient mice. 10 As a possibility, B cells may modulate myeloid cell phenotypes through the secretion of IL-10 and TNFa, thereby accelerating tumor progression.…”

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Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-celldepleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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“…This scenario is now changed as some in vitro studies have made clear that M1 macrophages are only cytotoxic to tumor cells but not to normal cells and, therefore, these M1 cells help in the early eradication of neotrasfromed cells [48][49][50][51][52][53]. Another way by which M1 macrophages exert their antitumor activity is through their antagonistic action on tumor-promoting action of TAMs, myeloid-derived suppressor cells (MDSCs), M2 macrophages, regulatory macrophages, and immature myeloid cells (i.e., all these cells suppress adaptive tumor-specific immune response and promote tumor growth and development) [54][55][56][57][58][59]. The exact role of macrophages in early stages of cancer is still controversial and yet to be determined.…”

Section: Classically Activated Macrophages (M1 Macrophages)mentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

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Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

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De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent

Cited by 736 publications

References 53 publications

Convergent pathways of macrophage polarization: The role of B cells

Convergent pathways of macrophage polarization: The role of B cells

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

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