Healthcare, Singapore (Commonwealth Union) – Macrophages, derived from the Greek word’s “macro” meaning large and “phagein” meaning to eat, aptly describe the primary function of these cells—devouring foreign invaders and cellular debris. However, their responsibilities extend far beyond mere phagocytosis. Macrophages are a type of white blood cell, belonging to the innate immune system, which serves as the body’s first line of defense against infections.
Derived from precursor cells in the bone marrow, macrophages migrate throughout the body, populating various tissues and organs. In each tissue, they adapt to local microenvironments and assume specialized roles. For instance, alveolar macrophages patrol the lungs, while Kupffer cells reside in the liver, ready to intercept blood-borne pathogens. In the brain, microglia act as the sentinels of the central nervous system.
Researchers at the Cancer Science Institute of Singapore (CSI), part of the National University of Singapore (NUS), made a significant discovery about a type of cancer called diffuse large B-cell lymphoma (DLBCL). They found out why some patients might get sick again after chemotherapy. The team, led by Assistant Professor Anand Jeyasekharan, studied special immune cells called “macrophages” in the cancer area. They learned that differences in these cells can affect how well patients recover.
While macrophages are essential for host defense, their dysregulation can contribute to various diseases. In conditions like chronic inflammation, autoimmune disorders, and cancer, macrophages can adopt aberrant phenotypes that promote tissue damage and disease progression. Alternatively, in infections such as tuberculosis, macrophages may become hijacked by pathogens, serving as reservoirs for microbial persistence.
These immune cells are old parts of the immune system that originally evolved to fight germs or clean up dead cells. They’re often found in cancers, but it wasn’t clear how important they were in lymphoma, according to the researchers.
They looked closely at different kinds of macrophages in DLBCL tumors. They used a new method known as Digital Spatial Profiling (DSP) at the CSI’s Microscope and Multiplex Assay (MMA) core facility. This helped them study macrophages and other cells in tumors and find out which kinds of macrophages were linked to patients getting sick again after treatment. This study showed that understanding different types of macrophages is crucial for treating this common and aggressive lymphoma. It can help predict how the disease will progress and lead to new treatments.
This research has big implications. Since macrophages are found in many cancers, similar methods can be used to see how they affect patients’ health.
Researchers of the study indicated that immunotherapy is seen as a new way to treat cancer, and most current treatments focus on a different kind of immune cell called T cells. But understanding macrophages better could lead to new drugs and treatments for DLBCL and other cancers by changing the cancer area.
Assistant Professor Jeyasekharan says, “Previously, studying immune cells in cancer was conducted in ‘bulk’, providing only a general overview of their presence in tumours. However, with technological advances now available, our team could examine the molecular features of macrophages with single-cell resolution while preserving their spatial context. We have identified different profiles of these ancient immune cells, which help in predicting the course of the disease more accurately. This step forward opens new possibilities for personalising stratification and treatment for DLBCL.”
The findings were unveiled in the March 8, 2024, edition of Nature Communications.
In upcoming endeavors, the team of Assistant Professor Jeyasekharan will undertake a comprehensive exploration of the role of macrophages in both biological and clinical contexts. Their objective is to elucidate the influence of these macrophage profiles on disease advancement and patient outcomes. This pursuit holds the promise of developing tailored diagnostic methods and therapeutic strategies tailored to individual disease traits. These advancements mark a significant stride in combating not just DLBCL but a spectrum of cancers.
In the intricate tapestry of the immune system, macrophages stand as formidable guardians, orchestrating a delicate balance between protection and regulation. Their multifaceted functions extend far beyond mere phagocytosis, encompassing roles in antigen presentation, cytokine secretion, and tissue homeostasis. As our understanding of macrophages deepens, so too does our ability to harness their potential for therapeutic benefit, offering hope for the treatment of a myriad of diseases, hence the findings of the study will give a clearer picture in macrophage research.
