New Study Links Macrophage Diversity with Patient Survival

Researchers at the National University of Singapore's Cancer Science Institute have significantly advanced our understanding of why diffuse large B-cell lymphoma, a specific type of cancer, often recurs after chemotherapy.

Under the direction of Assistant Professor Anand Jeyasekharan, the research team concentrated on a subset of immune cells known as “macrophages” in the environment surrounding cancer. The team found that differences in these cells are associated with the prognosis for patients, including survival and recovery.

Macrophages are an evolutionary ancient arm of the immune system that was originally developed to aid in the engulfment of dying cells or invasive microbes. Although macrophages are also commonly observed in cancers, it was unknown how relevant they were in lymphoma.

The study's key component was its in-depth examination of the variety of macrophages found in the DLBCL tumor environment. The team was able to analyze the molecular characteristics of macrophages within a complex mixture of cells in a tumor by using a novel technique called Digital Spatial Profiling (DSP), which is available at CSI's Microscope and Multiplex Assay (MMA) core facility.

This allowed them to identify subsets of macrophages linked to relapse following chemotherapy. This study demonstrated the significance of macrophage diversity in comprehending and managing this prevalent type of aggressive lymphoma, not only by improving the accuracy of disease progression prediction but also by identifying novel therapeutic targets.

This research has important ramifications. Given that macrophages are prevalent in a variety of cancers, comparable spatial methods can be employed to assess distinct macrophage patterns associated with patient outcomes.

The majority of existing immunotherapeutic strategies target T cells, a different type of cell, and immunotherapy is hailed as the next big thing in cancer treatment. Gaining knowledge about the diversity of macrophages may lead to the development of new medications and treatment strategies that target macrophages in order to alter the tumor environment in DLBCL and other cancers.

Previously, studying immune cells in cancer was conducted in 'bulk', providing only a general overview of their presence in tumors. 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 personalizing stratification and treatment for DLBCL.”

Anand Jeyasekharan, Assistant Professor, Cancer Science Institute of Singapore, National University of Singapore

The research was published in Nature Communications on March 8^th, 2024.

Future Work: Exploring the Impact of Macrophages in Biological and Clinical Settings

Moving forward, Assistant Professor Jeyasekharan's team aims to explore the biological and clinical implications of the macrophage profiles they have pinpointed, seeking to unravel their influence on disease advancement and patient outcomes.

Their endeavor could pave the way for novel diagnostic methodologies and tailored treatment modalities, personalized to the distinct attributes of individual patients' ailments. These strides mark a pivotal shift in combatting not just DLBCL but also various other cancer forms.