Research unlocks the role of macrophages in cancer relapse

Researchers from the Cancer Science Institute of Singapore (CSI) at the National University of Singapore (NUS), have achieved breakthroughs in understanding relapse after chemotherapy for a type of cancer known as diffuse large B-cell lymphoma (DLBCL). Led by Assistant Professor Anand Jeyasekharan, the study focused on a specific type of immune cells called "macrophages" found in the cancer's environment, and researchers discovered that variations in these cells are linked to how well patients might recover and survive.

Macrophages are evolutionarily an ancient arm of the immune system and initially evolved to help engulf invading microbes or dying cells. They are frequently noted in cancers as well, but their relevance in lymphoma was unclear.

The essence of the study lay in its deep dive into the diversity of macrophages within the tumor environment of DLBCL. By employing a novel method called Digital Spatial Profiling (DSP) available at CSI's Microscope and Multiplex Assay (MMA) core facility, the team was able to examine the molecular features of macrophages within a complex mixture of cells in a tumor, identifying subsets of macrophages associated with relapse after chemotherapy. This research showcased the importance of macrophage diversity in understanding and treating this common form of aggressive lymphoma, not only predicting the progression of the disease more accurately but also uncovering potential new therapeutic approaches.

The implications of this research are significant. As macrophages are common in several cancers, similar spatial approaches can be used to evaluate unique patterns in macrophages related to patient outcomes.

Immunotherapy is hailed as the next frontier in cancer treatment, and most current immunotherapeutic approaches target another type of cell - the T cell. The insights gained into macrophage diversity hold the promise of discovering novel drugs and therapeutic methods aimed at modifying the tumor environment in DLBCL and other cancers through tackling macrophages.

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 

The study was published in Nature Communications on 8 March 2024.

Future work: Exploring the impact of macrophages in biological and clinical settings

Moving forward, Asst Prof Jeyasekharan's team is set to delve deeper into the biological and clinical impacts of the macrophage profiles they have identified. Their goal is to understand how these profiles affect disease progression and patient survival. This could lead to the creation of new diagnostic tools and treatment options, specifically designed according to the unique characteristics of each patient's disease. Such advancements herald a new era in the fight against not only DLBCL but also other types of cancer.

Source:
Journal reference:

Liu, M., et al. (2024). Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma. Nature Communications. doi.org/10.1038/s41467-024-46220-z.

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