2 min readDiverse Immune Cell Profiles and Roles Found in Breast Cancer Resistance to Immunotherapy

Houston, TX — In recent years it has been increasingly appreciated that immune cells within the tumour microenvironment contribute to tumour progression and, importantly, to the tumor’s response to therapy. To better understand the specific roles different immune cell types play, a multi-institutional team led by researchers at Baylor College of Medicine profiled the immune cell composition of multiple murine models and clinical datasets of triple negative breast cancers. 

Focusing on two types of immune cells, neutrophils and macrophages, they found large diversity in the cells’ frequency, including neutrophil-enriched and macrophage-enriched groups whose functionality suggested potential roles in immunotherapy. The work highlights that heterogeneity of both tumour cells themselves and immune composition of the microenvironment are important considerations for therapy. The report appears in the journal Nature Cell Biology.

“We know that breast cancer is very heterogeneous. For many years we have recognized different subtypes of breast cancer, for instance, oestrogen receptor positive (ER+), ER- and triple negative, and these categories can be further divided into subcategories. To that, we now have to add the diversity of the immune cell component in the tumor microenvironment,” said corresponding author Dr. Xiang ‘Shawn’ Zhang, professor at the Lester and Sue Smith Breast Center and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.

With the goal of better understanding the role immune cells within tumours play in tumour growth and in response to therapy, Zhang and his colleagues conducted a series of analyses to characterize the immune cell composition of tumour microenvironments in eight murine models and in clinical datasets of triple negative breast cancers.

“Focusing on neutrophils and macrophages, we investigated whether different tumours had the same immune cell composition and whether seemingly similar immune components played the same role in tumour growth. Importantly, we wanted to find out whether differences in immune cell composition contributed to the tumors’ responses to immunotherapy,” said Zhang, a McNair Scholar at Baylor.

The researchers found large diversity in the frequency of neutrophils and macrophages among the tumour samples, including some tumours that preferentially attracted macrophages, while others attracted more neutrophils. The predominance of one cell type over the other can be explained in part by the type of molecules produced by the tumour. As Zhang explained, some tumours secrete molecules that attract macrophages, while other tumours produce other molecules that lure neutrophils to the tumour site.

Interestingly, macrophages and neutrophils seem to work against each other. 

“Once one type of cell starts accumulating in the tumour, the other will tend to stay away,” Zhang said. “What supports one type of cell, does not seem to support the other.” 

Exploring the roles macrophages and neutrophils play in tumour growth revealed that in some tumours macrophages favored tumour growth, while in others they helped control it. Neutrophils, on the other hand, tended to promote tumour growth.

“These findings are just the beginning. They highlight the need to investigate these two cellular types deeper. Under the name ‘macrophages’ there are many different cellular subtypes and the same stands for neutrophils,” Zhang said. “We need to identify at single cell level which subtypes favor and which ones disrupt tumour growth taking also into consideration tumour heterogeneity as both are relevant to therapy.”

Article adapted from a Baylor College of Medicine news release.

Publication: Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms. Kim, IS et al. Nature Cell Biology (August 26, 2019): Click here to view.

immune cells, Macrophages, microenvironment, Neutrophils, Tumour

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