Convergent pathways of macrophage polarization: The role of B cells

Abstract

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...

Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

“…Thus, the interaction of macrophages in different states of activation with antibodies and more generally with B cells is contextdependent and can result in promotion of carcinogenesis (e.g. [33,35,38,47]) or anti-tumor activity [3].…”

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs)

“…Among these, IL-10, prostaglandin E2 (PGE2), TGF-β, IL-6, CCL2, migration-stimulating factor (MSF) and CSF-1 were reported to induce M2-like polarization [ [54,[65][66][67][68]. Recent studies suggest that different circuits and cells, including innate immune cells and fibroblasts, participate in shaping TAM activities [13,[69][70][71][72] (Figure 2). As an example, in a model of mammary carcinoma, MDSCs were shown to contribute to tumor progression by suppressing Tcell activation and inducing an M2-like phenotype of TAMs [69].…”

Diversity and plasticity of mononuclear phagocytes

“…In particular, evidence indicates that pathways orchestrating TAM function [21][22][23] are diverse in tumours originating in different tissues and that there can be heterogeneity in mononuclear phagocytes in a given tumour [24,25].…”