Publications

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma. Although it is well established that PD-1-PD-L1 blockade activates T cells, little is known about the role that this pathway may have in tumour-associated macrophages (TAMs). Here we show that both mouse and human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models of cancer and with increasing disease stage in primary human cancers. TAM PD-1 expression correlates negatively with phagocytic potency against tumour cells, and blockade of PD-1-PD-L1 in vivo increases macrophage phagocytosis, reduces tumour growth and lengthens the survival of mice in mouse models of cancer in a macrophage-dependent fashion. This suggests that PD-1-PD-L1 therapies may also function through a direct effect on macrophages, with substantial implications for the treatment of cancer with these agents.

Endocrine disrupting chemicals, a group of exogenous chemicals that can interfere with hormone action in the body, have been implicated in disrupting endocrine function, which negatively affects human health and development. Endocrine disrupting chemicals are ubiquitously detected in consumer products, foods, beverages, personal care products, and household cleaning products. Due to concerns about their negative effects on human health, several professional health provider societies have recommended the reduction of common endocrine disrupting chemical exposures. The purpose of this review is to provide a brief overview of common endocrine disrupting chemicals (bisphenol A, phthalates, triclosan, polybrominated ethers, and parabens) and potential effects on child development and health. In addition, we aim to provide guidance and resources for pediatricians and other health care providers with counseling strategies to help patients to minimize exposures to common endocrine disrupting chemicals.