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Targeted Therapy of Interleukin-34 as a Promising Approach to Overcome Cancer Therapy Resistance
Giovanni Monteleone1,2, Eleonora Franzè1, Claudia Maresca1
1Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Abstract:
Chemotherapy and immunotherapy have markedly improved the management of several malignancies. However, not all cancer patients respond primarily to such therapies, and others can become resistant during treatment. Thus, identification of the factors/mechanisms underlying cancer resistance to such treatments could help develop novel effective therapeutic compounds. Tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) are major components of the suppressive tumor microenvironment and are critical drivers of immunosuppression, creating a tumor-promoting and drug-resistant niche. In this regard, therapeutic strategies to tackle immunosuppressive cells are an interesting option to increase anti-tumor immune responses and overcome the occurrence of drug resistance. Accumulating evidence indicates that interleukin-34 (IL-34), a cytokine produced by cancer cells, and/or TAMs act as a linker between induction of a tumor-associated immunosuppressive microenvironment and drug resistance. In this article, we review the current data supporting the role of IL-34 in the differentiation/function of immune suppressive cells and, hence, in the mechanisms leading to therapeutic resistance in various cancers.
Insights
Interleukin-34 (IL-34) drives cancer drug resistance by promoting immunosuppressive cells like tumor-associated macrophages (TAMs). Targeting IL-34 may overcome resistance and enhance anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chemotherapy and immunotherapy have improved cancer treatment, but primary resistance and acquired resistance remain significant challenges.
- The tumor microenvironment, particularly immunosuppressive cells such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs), plays a critical role in promoting tumor growth and therapeutic resistance.
- Developing strategies to overcome drug resistance by targeting these immunosuppressive cells is a key area of cancer research.
Purpose of the Study:
- To review the current literature on the role of interleukin-34 (IL-34) in cancer.
- To elucidate the mechanisms by which IL-34 contributes to the induction of an immunosuppressive tumor microenvironment.
- To explore the link between IL-34, immunosuppressive cells, and the development of resistance to cancer therapies.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of data on IL-34 production in various cancer types.
- Examination of the effects of IL-34 on the differentiation and function of TAMs, MDSCs, and Tregs.
- Investigation of the correlation between IL-34 levels and therapeutic resistance.
Main Results:
- IL-34 is produced by cancer cells and/or TAMs and influences the tumor microenvironment.
- IL-34 promotes the differentiation and function of immunosuppressive myeloid cells (TAMs and MDSCs).
- IL-34 signaling is implicated in the development of resistance to chemotherapy and immunotherapy across various malignancies.
Conclusions:
- IL-34 is a critical cytokine linking the immunosuppressive tumor microenvironment to therapeutic resistance.
- Targeting IL-34 or its downstream pathways presents a potential strategy to enhance anti-tumor immune responses and overcome drug resistance.
- Further research into IL-34's role could lead to novel therapeutic approaches for overcoming cancer treatment failure.
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