Macrophages groom cells to become cancerous

Good news! Cancer is history (soon)! This seems to be an interesting and novel discovery!

"Researchers have pinpointed a type of macrophage that reprograms pancreatic cells, making them cancerous. Using single-cell genomics, the team found that macrophages expressing a cytokine called interleukin-1β form an inflammatory loop with cancer cells. This “inflammatory reprogramming” happened early in the development of pancreatic cancer and “led to persistent transcriptional changes associated with disease progression and poor outcomes for patients”, the researchers write. Blocking the activity of interleukin-1β helped to control the growth of pancreatic tumour cells in mice."

From the abstract:

"Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC, but their diversity has prevented therapeutic exploitation. Here we combined single-cell and spatial genomics with functional experiments to unravel macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumour cells and interleukin-1β (IL-1β)-expressing TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E2 (PGE2) and tumour necrosis factor (TNF). Physical proximity with IL-1β+ TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor outcomes for patients. Blocking PGE2 or IL-1β activity elicited TAM reprogramming and antagonized tumour cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE2–IL-1β axis may enable preventive or therapeutic strategies for reprogramming of immune dynamics in pancreatic cancer."

nature briefing cancer

IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer | Nature (no public access)