The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

Ge, Zhe; Ding, Shuzhe

doi:10.3389/fonc.2020.590941

Cited by 124 publications

(84 citation statements)

References 193 publications

(201 reference statements)

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“…TAMs are important players in almost every step of metastasis formation [54]. Activation of Toll-like receptor 4 (TLR-4) on the surface of M2-like macrophages increases the level of IL-10, which promotes the EMT program, which plays an important role in the first steps of metastases [55]. EMT can also be induced by proinflammatory cytokines (IL-6, IL-1β, TNFα) [56] and TGFβ [57] released by TAMs (Figure 2).…”

Section: Tams In Tissue Invasion and Distant Metastasismentioning

confidence: 99%

The Role of Macrophages in Cancer Development and Therapy

Cendrowicz

Sas

Bremer

et al. 2021

Cancers

155

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Macrophages are critical mediators of tissue homeostasis and influence various aspects of immunity. Tumor-associated macrophages are one of the main cellular components of the tumor microenvironment. Depending on their activation status, macrophages can exert a dual influence on tumorigenesis by either antagonizing the cytotoxic activity of immune cells or, less frequently, by enhancing antitumor responses. In most situations, TAMs suppress T cell recruitment and function or regulate other aspects of tumor immunity. The importance of TAMs targeting in cancer therapy is derived from the strong association between the high infiltration of TAMs in the tumor tissue with poor patient prognosis. Several macrophage-targeting approaches in anticancer therapy are developed, including TAM depletion, inhibition of new TAM differentiation, or re-education of TAM activation for cancer cell phagocytosis. In this review, we will describe the role of TAMs in tumor development, including such aspects as protumorigenic inflammation, immune suppression, neoangiogenesis, and enhancement of tissue invasion and distant metastasis. Furthermore, we will discuss therapeutic approaches that aim to deplete TAMs or, on the contrary, re-educate TAMs for cancer cell phagocytosis and antitumor immunity.

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Section: Tams In Tissue Invasion and Distant Metastasismentioning

confidence: 99%

The Role of Macrophages in Cancer Development and Therapy

Cendrowicz

Sas

Bremer

et al. 2021

Cancers

155

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“…A specific example of such an influence exists in terms of CAFs, which are able to affect monocyte recruitment and polarization. Indeed, CAFs and TAMs are the main components of stromal cells (240)(241)(242)(243). Tumor associated macrophages display high level of plasticity.…”

Section: Reciprocal Interactionsmentioning

confidence: 99%

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Günaydın

2021

Front. Oncol.

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Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

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“…Based on the gene expression profiling analysis, high-risk neuroblastoma tissues express relatively high levels of CCL2, CXCL12, and TGFB1, which could influence the recruitment and polarization of myeloid cells (58)(59)(60)(61)(62)(63)(64)(65). We therefore addressed whether the various quantities of M2 TAMs and M-MDSCs linked to the variation in the cytokine/chemokine levels in the TME.…”

Section: The Immunosuppressive Cells In the Tme Of High-risk Neuroblastomamentioning

confidence: 99%

Clinical Relevance of CD4 Cytotoxic T Cells in High-Risk Neuroblastoma

2021

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Neuroblastoma is the most common extracranial childhood solid tumor. The majority of high-risk neuroblastoma is resistant/refractory to the current high intensity therapy, and the survival of these patients remains poor for the last three decades. To effectively treat these extremely unfavorable neuroblastomas, innovative immunotherapy approaches would be the most promising. In this article, we discuss the identity of tumor-infiltrating effector cells and immunosuppressive cells in high-risk neuroblastoma. Neuroblastoma is unique in that it expresses little or no classical HLA Class I and II. In contrast, high-risk neuroblastomas express the stress-responsive non-classical Class I, HLA-E molecule. HLA-E is the ligand of activating receptors NKG2C/E that are expressed on memory NK cells, CD8+T cells and CD4 CTLs. By examining a comprehensive RNA-seq gene expression dataset, we detected relatively high levels of CD4 expression in high-risk neuroblastoma tissues. The majority of CD4+ cells were CD3+, and thus they were likely tumor-associated CD4+T cells. In addition, high-level of both CD4 and NKG2C/E expression was associated with prolonged survival of the high-risk neuroblastoma patients, but CD8 levels were not, further suggesting that the CD4+ NKG2C/E+ T cells or CD4 CTL conferred cytotoxicity against the neuroblastoma cells. However, this T cell mediated- “protective effect” declined over time, in part due to the progressive formation of immunosuppressive tumor microenvironment. These observations suggest that to improve survival of high-risk neuroblastoma patients, it is essential to gain insights into how to enhance CD4 CTL cytotoxicity and control the immunosuppressive tumor microenvironment during the course of the disease.

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The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

Cited by 124 publications

References 193 publications

The Role of Macrophages in Cancer Development and Therapy

The Role of Macrophages in Cancer Development and Therapy

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Clinical Relevance of CD4 Cytotoxic T Cells in High-Risk Neuroblastoma

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