Tumor-Associated Macrophages as Treatment Targets in Oncology

By A. Mantovani, F. Marchesi, A. Malesci, L. Laghi, P. Allavena. Nature Reviews Clinical Oncology, 2017

3,492 citations recorded by the source corpus.

Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin–yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/bc9ca1c1a0cfb6f29a1f1dfe6d7eb2f807c0f5db

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Mantovani
2. J. Joyce
3. M. Locati
4. G. Curtale
5. Zena Werb
6. M. Pittet
7. Hugo Gonzalez
8. C. Roma-Rodrigues

In Oncology

1. A. Mantovani
2. Zena Werb
3. J. Joyce
4. M. Locati
5. M. Pittet
6. Muyue Yang
7. Hugo Gonzalez
8. C. Roma-Rodrigues

Citations in the corpus

• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “TAMs have been classified for alternately active (M2) macrophages within the TME, where they facilitate metastasis, angiogenesis, and suppression of the immune in a variety of cancers.(264) Compared to normal macrophages, the mitochondrial morphology of TAMs is more static and unstable.”
• Role of Bruton’s tyrosine kinase in B cells and malignancies (2018, background): “Since myeloid cells are important components of the tumor microenvironment and particularly tumor-associated macrophages contribute to cancer progression [22, 23], there is currently a considerable interest in BTK inhibition as an anti-cancer therapy not only in B cell leukemias but also in other he”
• Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures (2019, background): “org Cancer Immunol Res; 7(5) May 2019 745”
• Clinical relevance of tumour-associated macrophages (2022, background): “Several aspects currently being addressed include: (1) the complexity and diversity of macrophages, and whether distinct macrophage states can be identified; (2) whether and how different macrophage states contribute to disease progression or suppression; (3) the possibility of rational manipulation”
• Cholangiocarcinoma — evolving concepts and therapeutic strategies (2017, neutral): “Thus, targeting stromal cells, such as immuno suppressive TAMs or cancer­associated fibroblasts 156–158 , might prove to be a beneficial thera­ peutic strategy, particularly in combination with immuno therapy (FIG.”