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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
M2 macrophages and regulatory T cells in lethal prostate cancer
Ann Erlandsson1, Jessica Carlsson1, Marie Lundholm2
1Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Background:
Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs ) can contribute to cancer progression by suppressing the anti-tumor immune response. This study investigated the number of CD163-positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs .
Methods:
This nested case-control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163-positive M2 macrophages and FOXP3/CD4-positive Tregs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and Tregs were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.
Results:
The number of M2 macrophages and Tregs showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.
Conclusions:
Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.
Insights
High numbers of M2 macrophages in prostate cancer tissue correlate with increased risk of death from the disease. These findings suggest M2 macrophages may contribute to an immunosuppressive tumor environment, impacting lethal prostate cancer outcomes.
Area of Science:
- Oncology
- Immunology
Background:
- Prostate cancer (PCa) is a globally prevalent malignancy.
- Inflammatory cells, including M2 macrophages and regulatory T cells (Tregs), are implicated in cancer progression by suppressing anti-tumor immunity.
Purpose of the Study:
- To investigate the density of CD163-positive M2 macrophages in PCa tissue.
- To assess the correlation and interaction between M2 macrophages and Tregs in the PCa microenvironment.
Main Methods:
- A nested case-control study involving 225 PCa cases and 367 controls.
- Immunohistochemistry used to identify M2 macrophages and Tregs (FOXP3/CD4) in PCa tissue.
- Statistical analyses included Spearman correlation, likelihood tests, and logistic regression to evaluate associations with lethal PCa.
Main Results:
- A significant correlation was observed between M2 macrophages and Tregs (P < 0.001), but no significant interaction.
- High M2 macrophage counts were associated with a 1.93-fold increased odds of lethal PCa (95% CI: 1.23-3.03).
- Elevated M2 macrophage levels predicted a poorer prognosis in cases with intermediate Gleason scores (3+4 and 4+3).
Conclusions:
- Increased M2 macrophage presence in prostate tumors is linked to a higher likelihood of PCa mortality.
- M2 macrophages, potentially alongside Tregs, may foster an immunosuppressive tumor milieu, promoting PCa progression and lethality.
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