The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Yang, Qiyao; Guo, Ningning; Zhou, Yi; Chen, Jiejian; Wei, Qichun; Han, Min

doi:10.1016/j.apsb.2020.04.004

Cited by 233 publications

(199 citation statements)

References 178 publications

(114 reference statements)

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“…These cells are believed to act as tumor-associated macrophages, a concept that has been developed in other cancer types. It is suggested that the tumor microenvironment is able to recruit macrophages into functioning as supportive helpers regarding tumor growth [ 11 ]. With the rising significance of immunotherapeutic approaches in cancer and the first insights into vestibular schwannomas, the role of inflammation in vestibular schwannoma growth needs to be investigated in greater detail with higher case numbers.…”

Section: Introductionmentioning

confidence: 99%

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

Gonçalves

Suhm

Ries

et al. 2021

Cancers

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Most patients with vestibular schwannomas can be cured with microsurgical resection, or tumor growth can be stabilized by radiotherapy in certain cases. Recurrence is rare but usually difficult to treat. Treatment alternatives to local therapies are not established. There is growing evidence of the role of inflammatory processes in schwannomas, which may be exploitable by targeted innovative therapies. To further define the impact of inflammation with tumor growth in vestibular schwannoma, we performed immunohistochemical analyses of CD3, CD8, CD68 and CD163 to assess lymphocyte and macrophage infiltration in 923 tumor tissue samples of surgically resected vestibular schwannomas. An inflammatory score was compared with tumor size and volumetric growth. We observed a significantly larger preoperative tumor size with increased expression rates of CD3, CD8, CD68 and CD163 (p < 0.0001, p < 0.0001, p = 0.0015 and p < 0.0001, respectively), but no differences in percentual volumetric tumor growth. When all four markers were combined as an inflammatory score, tumors with high inflammatory infiltration showed slower percentual growth in a multivariate analysis, including MIB1 expression (p = 0.0249). We conclude that inflammatory cell infiltration increases with larger tumor size but is associated with slower percentual volumetric tumor growth.

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Section: Introductionmentioning

confidence: 99%

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

Gonçalves

Suhm

Ries

et al. 2021

Cancers

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show abstract

“…IL-4 and IL-13 are the Th2 cytokines that typically induce M2a macrophages; LPS and IL-1 promote the differentiation of M2b-TAMs; IL-10 and glucocorticoids can elicit the M2c form of active macrophages. In turn, the different subtypes of M2-TAMs, induced by different tumor-derived factors, correspond to various grades of immunosuppressive functions: M2a-TAMs inhibit the Th1 but activate the Th2 immune response, while both M2b and M2c macrophages exhibit general anti-immunity effects [ 17 ].…”

Section: From Circulating Monocytes To Tumor-associated Macrophagementioning

confidence: 99%

Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma

Ceci

Atzori

Lacal

et al. 2020

Cancers

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Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. Thus, strategies targeting M2-TAMs have been suggested to synergize with immune checkpoint blockade. This review recapitulates the molecular mechanisms by which M2-TAMs promote cancer immune evasion, with focus on the potential cross-talk between pharmacological interventions targeting M2-TAMs and ICIs for melanoma treatment.

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“…TAMs in the vicinity of progressive tumors usually acquire an M2 phenotype, which enables them to perform immunosuppressive and tumor-promoting functions [ 15 , 16 ]. Once recruited by tumor cells secreting chemoattractants, TAMs are educated in TME.…”

Section: Introductionmentioning

confidence: 99%

Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1

Kim

Park

et al. 2021

Antioxidants

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Tumor-associated macrophages (TAMs) represent one of the most abundant components of the tumor microenvironment and play important roles in tumor development and progression. TAMs display plasticity and functional heterogeneity as reflected by distinct phenotypic subsets. TAMs with an M1 phenotype have proinflammatory and anti-tumoral properties whereas M2-like TAMs exert anti-inflammatory and pro-tumoral functions. Tumor cell debris generated during chemotherapy can stimulate primary tumor growth and recurrence. According to our previous study, phagocytic engulfment of breast tumor cell debris by TAMs attenuated chemotherapeutic efficacy through the upregulation of heme oxygenase-1 (HO-1). To verify the impact of HO-1 upregulation on the profile of macrophage polarization during cytotoxic therapy, we utilized a syngeneic murine breast cancer (4T1) model in which tumor bearing mice were treated with paclitaxel (PTX). PTX treatment markedly downregulated the surface expression of the M1 marker CD86 in infiltrated TAMs. Notably, there were significantly more cytotoxic CD8+ T cells in tumors of mice treated with PTX plus the HO-1 inhibitor, zinc protophorphyrin IX (ZnPP) than in mice treated with PTX alone. Interestingly, the tumor-inhibiting efficacy of PTX and ZnPP co-treatment was abrogated when macrophages were depleted by clodronate liposomes. Macrophage depletion also decreased the intratumoral CD8+ T cell population and downregulated the expression of Cxcl9 and Cxcl10. The expression of the M1 phenotype marker, CD86 was higher in mice injected with PTX plus ZnPP than that in mice treated with PTX alone. Conversely, the PTX-induced upregulation of the M2 marker gene, Il10 in CD11b+ myeloid cells from 4T1 tumor-bearing mice treated was dramatically reduced by the administration of the HO-1 inhibitor. Genetic ablation of HO-1 abolished the inhibitory effect of 4T1 tumor cell debris on expression of M1 marker genes, Tnf and Il12b, in LPS-stimulated BMDMs. HO-1-deficient BMDMs exposed to tumor cell debris also exhibited a diminished expression of the M2 macrophage marker, CD206. These findings, taken all together, provide strong evidence that HO-1 plays a pivotal role in the transition of tumor-inhibiting M1-like TAMs to tumor-promoting M2-like ones during chemotherapy.

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The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Cited by 233 publications

References 178 publications

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort

Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma

Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1

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