Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma.

BACKGROUND

It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity.

OBJECTIVE

To investigate the association between infiltration of CD163 M2 macrophages and CD4FOXP3 Tregs with clinical outcomes in renal cell carcinoma patients.

DESIGN SETTING AND PARTICIPANTS

A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163 M2 macrophage and CD4FOXP3 Treg infiltration by immunohistochemistry.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Associations between clinicopathological features and infiltration of CD163 M2 macrophages and/or CD4FOXP3 Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.

RESULTS AND LIMITATIONS

We found that infiltration of CD163 M2 macrophages and CD4FOXP3 Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163 M2 macrophages and CD4FOXP3 Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation.

CONCLUSIONS

Infiltration of CD163 M2 macrophages and CD4FOXP3 Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome.

PATIENT SUMMARY

The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.