Macrophage-Based Approaches for Cancer Immunotherapy

Anderson, Nicholas; Minutolo, Nicholas G.; Gill, Saar; Klichinsky, Michael

doi:10.1158/0008-5472.can-20-2990

Cited by 417 publications

(342 citation statements)

References 119 publications

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“…Previous studies using experimental models have shown that depletion of macrophages can inhibit tumor progression and metastasis. On the other hand, it is also known that macrophages inherent anti-tumor potential through antigen presentation and secretion of anti-tumor factors, active T cells, and NK cells [ 9 , 88 ]. Hence, it is necessary to clarify their functions by determining the mechanisms of macrophage polarization and the functions of macrophages during tumor development and progression ( Figure 3 ).…”

Section: Tams Are Involved In Tumor Progressionmentioning

confidence: 99%

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Wang

Yung

Ngan

et al. 2021

IJMS

128

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Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.

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Section: Tams Are Involved In Tumor Progressionmentioning

confidence: 99%

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Wang

Yung

Ngan

et al. 2021

IJMS

128

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“…Macrophages exhibit a high degree of plasticity when exposed to various environmental stimuli. They are polarized to one of two opposite types in vitro , classically activated M1 macrophages that can be induced by lipopolysaccharide (LPS), interferon-γ (IFN-γ), or colony-stimulating factor 2 (CSF2, also known as granulocyte-macrophage colony-stimulating factor) or alternatively activated M2 macrophages that can be induced by interleukin 4 (IL4), IL13, or CSF1 (also known as macrophage colony-stimulating factor) ( 1 – 3 ). M2 macrophages are further categorized as M2a, M2b, M2c, and M2d cells upon stimulation of different M2 drivers ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…M2 macrophages are further categorized as M2a, M2b, M2c, and M2d cells upon stimulation of different M2 drivers ( 4 ). Generally, M1 macrophages exert an immune protective role via the secretion of pro-inflammatory cytokines, whereas M2 macrophages are characterized by anti-inflammatory properties, which contribute to tissue remodeling and tumor progression ( 3 ). Multiple co-stimulatory and antigen-presenting molecules are expressed on the cell membrane of antigen-presenting cells (APCs), including macrophages.…”

Section: Introductionmentioning

confidence: 99%

Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1

et al. 2021

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Classically activated M1 macrophages and alternatively activated M2 macrophages are two polarized subsets of macrophages at the extreme ends of a constructed continuum. In the field of cancer research, M2 macrophage reprogramming is defined as the repolarization of pro-tumoral M2 to anti-tumoral M1 macrophages. It is known that colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) and CSF2/CSF2R signaling play important roles in macrophage polarization. Targeting CSF1/CSF1R for M2 macrophage reprogramming has been widely performed in clinical trials for cancer therapy. Other targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), and PI3Kγ. Although macrophages are involved in innate and adaptive immune responses, M1 macrophages are less effective at phagocytosis and antigen presenting, which are required properties for the activation of T cells and eradication of cancer cells. Similar to T and dendritic cells, the “functionally exhausted” status might be attributed to the high expression of programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1). PD-L1 is expressed on both M1 and M2 macrophages. Macrophage reprogramming from M2 to M1 might increase the expression of PD-L1, which can be transcriptionally activated by STAT3. Macrophage reprogramming or PD-L1/PD-1 blockade alone is less effective in the treatment of most cancers. Since PD-L1/PD-1 blockade could make up for the defect in macrophage reprogramming, the combination of macrophage reprogramming and PD-L1/PD-1 blockade might be a novel treatment strategy for cancer therapy.

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“…With this strategy, developed by Klichinsky et al. in 2016 ( 100 ), CAR-modified macrophages eliminated tumor cells more effectively than non-CAR-modified M1-like macrophages in vitro and in vivo ( 101 ). The creators of this technology have developed the company CARISMA therapeutics which has an ongoing phase I clinical trial on CAR-M for treating HER2- overexpressing solid tumors (including squamous carcinoma) (NCT04660929).…”

Section: Macrophages As Drug Delivery Vehiclesmentioning

confidence: 99%

Pro-Tumorigenic Macrophage Infiltration in Oral Squamous Cell Carcinoma and Possible Macrophage-Aimed Therapeutic Interventions

Bruna

Scodeller

2021

Front. Oncol.

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In Oral Squamous Cell Carcinomas (OSCC), as in other solid tumors, stromal cells strongly support the spread and growth of the tumor. Macrophages in tumors (tumor-associated macrophages or “TAMs”), can swing between a pro-inflammatory and anti-tumorigenic (M1-like TAMs) state or an anti‐inflammatory and pro-tumorigenic (M2-like TAMs) profile depending on the tumor microenvironment cues. Numerous clinical and preclinical studies have demonstrated the importance of macrophages in the prognosis of patients with different types of cancer. Here, our aim was to review the role of M2-like TAMs in the prognosis of patients with OSCC and provide a state of the art on strategies for depleting or reprogramming M2-like TAMs as a possible therapeutic solution for OSCC. The Clinical studies reviewed showed that higher density of CD163+ M2-like TAMs associated with worse survival and that CD206+ M2-TAMs are involved in OSCC progression through epidermal growth factor (EGF) secretion, underlining the important role of CD206 as a marker of OSCC progression and as a therapeutic target. Here, we provide the reader with the current tools, in preclinical and clinical stage, for depleting M2-like TAMs, re-educating them towards M1-like TAMs, and exploiting TAMs as drug delivery vectors.

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Macrophage-Based Approaches for Cancer Immunotherapy

Cited by 417 publications

References 119 publications

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1

Pro-Tumorigenic Macrophage Infiltration in Oral Squamous Cell Carcinoma and Possible Macrophage-Aimed Therapeutic Interventions

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