Regulatory T Cells and Tumor-Associated Macrophages Colocalize in Pediatric Hepatoblastoma.

INTRODUCTION

Hepatoblastoma (HB) is the most common liver cancer in infants and children. Human HB tumor specimens were analyzed to identify a distinct population of tumor-associated macrophages (TAMs). We queried whether TAMs cooperate with other regulatory immune populations (e.g., regulatory T cells [Tregs]) to establish an immunoregulatory environment that promotes HB formation.

METHODS

Immunohistochemistry was used to identify CD68+ TAMs and CD4+FoxP3+ Tregs in nine HB tumors and adjacent normal liver. After receiving neoadjuvant chemotherapy, regions of viable and nonviable tumor (treatment effect) were identified. Clusters of TAMs and Tregs were defined by density and size and we calculated the percentage of TAMs and Tregs that colocalize with the other cell type.

RESULTS

HB tumor specimens from nine patients were analyzed and 313 distinct clusters were identified of which 56% were Treg and 44% were TAM clusters. We identified a total of 68 regions where TAM and Treg clusters overlapped; no TAM or Treg clusters were identified in adjacent normal tumor. Tregs and TAMs tended to cluster within viable tumor. Half of the TAM/Treg coclusters were identified at regions that bordered viable and nonviable tumor.

CONCLUSIONS

Clusters of TAMs and Tregs were found in human HB tumor and were not identified in normal liver. While colocalization of these populations was not uniform, regulatory niches may favor viable HB tumor supporting our hypothesis that immunoregulatory populations may establish niches to suppress immune signals and promote HB by blunting the treatment effect of neoadjuvant chemotherapy.