In a recent study involving human breast cancer cells, researchers have potentially pinpointed specific immune white blood cells that seem to closely interact with breast cancer cells likely to spread. This discovery, spotlighting a type of white blood cell known as a macrophage, may pave the way for new immunotherapy targets aimed at eliminating cancer cells associated with advancing disease.
In a recent study involving human breast cancer cells, researchers have potentially pinpointed specific immune white blood cells that seem to closely interact with breast cancer cells likely to spread. This discovery, spotlighting a type of white blood cell known as a macrophage, may pave the way for new immunotherapy targets aimed at eliminating cancer cells associated with advancing disease.
Findings from this research were published online on August 20 in the journal Oncogene.
The research team from the Johns Hopkins Kimmel Cancer Center employed advanced imaging techniques to observe the arrangement of individual cells within tumors, building on previous work by their colleagues at the Johns Hopkins Giovanis Institute, who had identified biomarkers on breast cancer cells prone to spreading.
“One of the most significant advancements in cancer therapy is immunotherapy — treatments that enhance the immune system’s ability to combat tumors,” remarks Andrew Ewald, Ph.D., a professor and director at the Department of Cell Biology and the Johns Hopkins Giovanis Institute. He adds that, as of now, these therapies are effective only for a limited number of patients, highlighting the need for more specific cellular targets to enhance their overall efficacy.
The researchers concentrated on immune cells because they interact closely with cancer cells, explains Ewald. Such interactions initiate a kind of “handshake” process that enables immune cells like macrophages to recognize encountered cells.
During these interactions, the immune system can categorize some cells as “foreign,” marking them for destruction, while allowing others to remain unharmed. However, cancer cells often possess the capability to disguise themselves, deceiving the immune system and evading elimination, allowing them to proliferate and spread.
To identify the cells in proximity to breast cancer cells, the Johns Hopkins scientists examined primary and metastatic breast cancer tissues from 24 patients who donated their tissues posthumously to a rapid autopsy initiative facilitated by Johns Hopkins researchers.
Won Jin Ho, M.D., an oncologist and imaging specialist at the Kimmel Cancer Center, utilized a technique known as mass cytometry to analyze and map the various cells present in the tissue samples.
While other scientists have mapped cells in similar tissues, the Johns Hopkins team emphasized their study on the cells closest to those most likely to spread, rather than the average surrounding cells.
With hundreds of cells found within a single tissue sample, Ho compares the analysis of dissociated cells to making a smoothie, where everything is mixed, whereas imaging allows for clarity on spatial arrangements. Ho is an assistant professor of oncology and heads the Mass Cytometry Facility at Johns Hopkins.
Ewald, along with former postdoctoral researcher Eloïse Grasset, Ph.D., who is currently with the National Centre for Scientific Research in France, had earlier identified a common biomarker signature associated with breast cancer cells that are likely to metastasize.
The researchers utilized 36 of these biomarkers to locate metastasis-initiating cells and identify nearby cells — both those in immediate proximity (approximately 10-20 microns), as well as those slightly further out and even more distant cells.
“What stood out to us among the immune system cells was a particular subgroup of macrophages that are either very close to or in contact with metastasis-initiating cells in both primary and metastatic tissue samples,” states Ho. These macrophage subsets constitute a small fraction, only about 1%-5%, of the total cells in the tumor.
The research team validated their findings by confirming the presence of these essential macrophage subsets in over 100 additional breast cancer samples collected from a tumor bank, demonstrating that such distinct macrophage types are indeed part of the breast cancer microenvironment.
Macrophages, a type of white blood cell, can engulf and eliminate “foreign” cells independently, but they can also summon other immune cells to target those identified as alien to the body. Ho points out that prior studies have linked the presence of numerous macrophages in tumors to poorer prognoses and reduced responses to immunotherapy.
“As discovery-driven scientists, we are seeking methods to alter the immune system’s spatial arrangement within the environment surrounding cancer cells,” says Ewald. “In the future, we could develop biological therapies to reshape how groups of cancer cells are organized.”
Other contributors to the study include Atul Deshpande, Jae Lee, Yeonju Cho, Sarah Shin, Erin Coyne, Alexei Hernandez, Xuan Yuan, Zhehao Zhang, and Ashley Cimino-Mathews from Johns Hopkins.
The researchers associated with Johns Hopkins University declared no conflicts of interest according to university policies.
This research was funded by the National Institutes of Health National Cancer Institute (U01CA284090, U54CA268083, P30CA006973, R21CA264004), the Hope Scarves Foundation, the Jayne Koskinas Ted Giovanis Foundation, the Breast Cancer Research Foundation, the Emerald Foundation, Break Through Cancer, and the Maryland Cancer Moonshot.
