Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy

Cotechini, Tiziana; Atallah, Aline; Grossman, Arielle

doi:10.3390/cells10040960

Cited by 40 publications

(30 citation statements)

References 258 publications

(353 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently the number of TAMs is associated with a poor prognosis for several types of cancer (44,(111)(112)(113)(114). TAMs can originate from tissue resident macrophages or from circulating monocytes that infiltrate the tumor (115). How TAMs acquire this pro-tumorigenic phenotype is still largely unknown, but several studies have shown that their migration and immunesuppressive activity can be greatly affected by the composition and mechanical properties of the surrounding ECM, and in particular by collagen (86,(116)(117)(118).…”

Section: Collagen-mediated Modulation Of Macrophage Activitymentioning

confidence: 99%

Immune Modulatory Properties of Collagen in Cancer

2021

View full text Add to dashboard Cite

During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

show abstract

Section: Collagen-mediated Modulation Of Macrophage Activitymentioning

confidence: 99%

Immune Modulatory Properties of Collagen in Cancer

2021

View full text Add to dashboard Cite

show abstract

“…Depleting or stabilizing MCs has been hypothesized to enhance anti-cancer mechanisms ( 76 ). As with MCs, it was hypothesized tumor macrophage depletion and/or inhibition was also a plausible strategy for anti-cancer therapeutics ( 77 ). Now, macrophages are at the forefront of translational ACT research and are poised to become another cell in the arsenal of cancer cell immunotherapies ( 78 ).…”

Section: Discussionmentioning

confidence: 99%

Human Tumor Targeted Cytotoxic Mast Cells for Cancer Immunotherapy

et al. 2022

View full text Add to dashboard Cite

The diversity of autologous cells being used and investigated for cancer therapy continues to increase. Mast cells (MCs) are tissue cells that contain a unique set of anti-cancer mediators and are found in and around tumors. We sought to exploit the anti-tumor mediators in MC granules to selectively target them to tumor cells using tumor specific immunoglobin E (IgE) and controllably trigger release of anti-tumor mediators upon tumor cell engagement. We used a human HER2/neu-specific IgE to arm human MCs through the high affinity IgE receptor (FcεRI). The ability of MCs to bind to and induce apoptosis of HER2/neu-positive cancer cells in vitro and in vivo was assessed. The interactions between MCs and cancer cells were investigated in real time using confocal microscopy. The mechanism of action using cytotoxic MCs was examined using gene array profiling. Genetically manipulating autologous MC to assess the effects of MC-specific mediators have on apoptosis of tumor cells was developed using siRNA. We found that HER2/neu tumor-specific IgE-sensitized MCs bound, penetrated, and killed HER2/neu-positive tumor masses in vitro. Tunneling nanotubes formed between MCs and tumor cells are described that parallel tumor cell apoptosis. In solid tumor, human breast cancer (BC) xenograft mouse models, infusion of HER2/neu IgE-sensitized human MCs co-localized to BC cells, decreased tumor burden, and prolonged overall survival without indications of toxicity. Gene microarray of tumor cells suggests a dependence on TNF and TGFβ signaling pathways leading to apoptosis. Knocking down MC-released tryptase did not affect apoptosis of cancer cells. These studies suggest MCs can be polarized from Type I hypersensitivity-mediating cells to cytotoxic cells that selectively target tumor cells and specifically triggered to release anti-tumor mediators. A strategy to investigate which MC mediators are responsible for the observed tumor killing is described so that rational decisions can be made in the future when selecting which mediators to target for deletion or those that could further polarize them to cytotoxic MC by adding other known anti-tumor agents. Using autologous human MC may provide further options for cancer therapeutics that offers a unique anti-cancer mechanism of action using tumor targeted IgE’s.

show abstract

“… 29 , 30 , 31 , 32 Obviously, these macrophages are one of the earliest cells interacting with transformed cells in the process of tumor formation. 33 Monocyte-derived TAMs originate from circulating monocytes in the peripheral circulation. In response to the internal environment after tumor formation, these cells are recruited to the TME and rapidly differentiate into macrophages.…”

Section: Macrophages In Tumorsmentioning

confidence: 99%