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Targeting IL-34/MCSF-1R Axis in Colon Cancer.

Giovanni Monteleone¹, Claudia Maresca¹, Marco Colella¹

¹Department of Systems Medicine, University of Rome "TOR VERGATA", Rome, Italy.

Frontiers in Immunology

|July 15, 2022

Summary

Interleukin-34 (IL-34) and its receptor, macrophage colony-stimulating factor-1 receptor (MCSF-1R), promote colorectal cancer (CRC) growth and resistance to therapies. Targeting this axis may offer new CRC treatment strategies.

Keywords:

MCSF-1 cancer-associated fibroblasts colorectal carcinoma tumor microenvironment tumor-associated macrophages

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Area of Science:

Oncology
Immunology
Molecular Biology

Background:

Colorectal carcinoma (CRC) remains a deadly cancer, particularly when metastatic, due to limited treatment efficacy.
The tumor microenvironment, including cytokines like Interleukin-34 (IL-34), significantly influences CRC progression.
IL-34 and its receptor, macrophage colony-stimulating factor-1 receptor (MCSF-1R), are implicated in CRC cell behavior and immune cell modulation.

Purpose of the Study:

To review the current understanding of IL-34 and MCSF-1R involvement in colorectal cancer.
To highlight the role of the IL-34/MCSF-1R axis in regulating tumor-associated macrophages (TAMs).
To explore the potential of targeting the IL-34/MCSF-1R pathway for CRC therapeutic intervention.

Main Methods:

Literature review of existing studies on IL-34 and MCSF-1R in CRC.
Analysis of data on the expression and function of IL-34 and MCSF-1R in CRC cells and the tumor microenvironment.
Examination of evidence linking the IL-34/MCSF-1R axis to TAMs, chemotherapy resistance, and immunotherapy response.

Main Results:

IL-34 is highly produced in human CRC by both cancer and non-tumoral cells.
The IL-34/MCSF-1R axis promotes pro-tumoral functions, including regulation of TAMs.
Overexpression of MCSF-1R is observed in CRC cells, TAMs, and cancer-associated fibroblasts.
IL-34/MCSF-1R signaling contributes to cancer cell resistance to chemotherapy and immunotherapy.

Conclusions:

The IL-34/MCSF-1R axis plays a critical role in colorectal cancer progression and treatment resistance.
Targeting IL-34 or MCSF-1R presents a promising therapeutic strategy for CRC.
Further research into the IL-34/MCSF-1R pathway could lead to novel treatments for colorectal cancer.