Tumour-associated macrophages are associated with poor prognosis and programmed death ligand 1 expression in oesophageal cancer.

INTRODUCTION

Tumour-associated macrophages (TAMs) in tumour microenvironments promote cancer cell proliferation, immunosuppression and angiogenesis, leading to tumour growth and metastasis. TAMs have become increasingly recognised as a cancer therapy target, such as in combination therapy with an immunity checkpoint inhibitor. However, the clinical and prognostic features of TAMs, and the relationship between TAMs and programmed death ligand 1 (PD-L1), remain unexplored in oesophageal cancer.

METHODS

Using a non-biased database of 305 resected oesophageal cancer preparations, we evaluated the expression of two M2-like macrophage markers (CD163 and CD204) and PD-L1 on tumour cells by immunostaining. Through in vitro assays, we examined how TAMs influence phenotypic malignancy and PD-L1 expression.

RESULTS

High density of CD163 (n = 160) or CD204 (n = 146) was associated with significantly worse overall survival than low expression (log rank P = 0.0025 and 0.018 for CD163 and CD204, respectively). The prognostic effect of TAMs was not significantly modified by any clinical factors (P > 0.05 for all interactions). High TAM density was significantly associated with increased PD-L1 expression. In in vitro assays, cell invasion and migration ability were significantly more upregulated in oesophageal cancer cell lines cocultured with activated macrophages than in control cell lines. Coculture with activated macrophages elevated the PD-L1 expression in cancer cells.

CONCLUSIONS

High TAM density in oesophageal cancer tissues was associated with shorter survival, suggesting a prognostic biomarker role for TAMs. TAMs also increase PD-L1 expression in tumour cells. Given the significant interest in cancer immunotherapies targeting TAMs and PD-L1, the current findings should have considerable clinical implications.