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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Immunoglobulin-like transcript 5 polarizes M2-like tumor-associated macrophages for immunosuppression in non-small
Huijun Xu1,2, Xuebing Fu3, Shuyun Wang4
1Jinan Central Hospital, Shandong University, Jinan, Shandong, China.
Abstract:
Immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm of non-small cell lung cancer (NSCLC) over the last decade. Despite notable therapeutic advancements in responders, the response rate remains limited owing to the immunosuppressive tumor microenvironment (TME). Therefore, to improve the efficacy of ICIs, it is essential to explore alternative targets or signals that mediate immunosuppression. Immunoglobulin-like transcript (ILT) 5 is a negative regulator of immune activation in myeloid cells. However, the expression and function of ILT5 in NSCLC remain unknown. Here, we found that ILT5 was highly expressed in tumor-associated macrophages (TAMs) of NSCLC tissues and predicted poor patient survival. Functionally, ILT5 induces the M2-like polarization of TAMs, which subsequently decreases the density of T cells, and increases FOXP3+T cell accumulation, leading to an immunosuppressive TME. The combination of ILT5 expression with M2-like TAM density is a more reliable biomarker of patient survival than ILT5 expression alone. ILT5 knockout mitigates the reprogramming of TAM and T cell subsets toward immunosuppressive phenotypes and inhibits tumor growth in vivo. These findings highlight that ILT5 is a potential immunotherapeutic target and a promising prognostic biomarker for NSCLC.
Insights
Immunoglobulin-like transcript 5 (ILT5) promotes an immunosuppressive tumor microenvironment in non-small cell lung cancer (NSCLC). Targeting ILT5 in tumor-associated macrophages may improve immunotherapy efficacy for NSCLC patients.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancer (NSCLC) treatment.
- Limited response rates to ICIs are often due to the immunosuppressive tumor microenvironment (TME).
- Identifying novel targets to overcome TME-mediated immunosuppression is crucial for enhancing ICI efficacy.
Purpose of the Study:
- To investigate the expression and function of Immunoglobulin-like transcript 5 (ILT5) in NSCLC.
- To determine the role of ILT5 in shaping the tumor microenvironment and its impact on patient survival.
- To evaluate ILT5 as a potential therapeutic target and prognostic biomarker in NSCLC.
Main Methods:
- Analysis of ILT5 expression in NSCLC tissues and its correlation with patient survival.
- Functional studies to elucidate ILT5's role in macrophage polarization and T cell infiltration.
- In vivo experiments using ILT5 knockout models to assess tumor growth inhibition.
Main Results:
- ILT5 is highly expressed in tumor-associated macrophages (TAMs) in NSCLC and is associated with poor patient survival.
- ILT5 promotes M2-like polarization of TAMs, leading to decreased T cell density and increased FOXP3+ T cell accumulation, creating an immunosuppressive TME.
- Combined ILT5 expression and M2-like TAM density serve as a more robust prognostic biomarker than ILT5 alone.
- ILT5 knockout suppressed TAM reprogramming, reduced immunosuppressive T cell subsets, and inhibited tumor growth in vivo.
Conclusions:
- ILT5 plays a significant role in promoting an immunosuppressive TME in NSCLC by modulating TAMs and T cell populations.
- ILT5 represents a promising novel immunotherapeutic target for enhancing ICI efficacy in NSCLC.
- ILT5, particularly in conjunction with M2-like TAM density, is a valuable prognostic biomarker for NSCLC patients.
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