Insights into the Landscape of the Breast Tumor Microenvironment

Researchers characterized the tumor microenvironment of thousands of early and metastatic breast cancer cells from a small group of patients and presented the insights at the 2018 San Antonio Breast Cancer Symposium (SABCS) in Texas.¹

Using a multidimensional single cell genomics approach, study researchers examined the tumor microenvironment of a cohort of 22 patients with early and metastatic breast cancers. More than 125,000 cells were obtained from patients and analyzed with single cell RNA-sequencing.

The analysis revealed that malignant cells had “remarkable intratumoural heterogeneity for canonical breast cancer features,” the authors reported. Features of interest included intrinsic subtype, hormone receptor expression, and drug targets.

Further, cancer-associated fibroblasts showed heterogeneity between primary and metastatic cancer sites. The study researchers also found a myofibroblast-like subset and an inflammatory-mediator subset and proposed that these subsets have “multifaceted roles” in regulating malignancy and tumor immunity.

Researchers used CITE-Seq to assess cell surface immune markers and checkpoint proteins. They also created a new method called RAGE-Seq to follow lymphocyte clonal dynamics and found clonal expansion and trafficking of CD4+ and CD8+ T lymphocytes among the lymph nodes, blood, and tumor site. Conversely, B cells were observed as polyclonal, which, according to the researchers, suggests “an absence of antigen-dependent clonal expansion.”

“This data provides by far the most extensive insights into the cellular landscape of breast cancer and will reveal new biomarkers and opportunities for stromal- and immune-based therapy,” the authors concluded.

Read more of Cancer Therapy Advisor‘s coverage of the SABCS 2018 meeting by visiting the conference page.

Reference

1. Swarbrick A, Wu SZ, Roden D, Al-Eryani G, O’Toole S, Lim E. Landscape of the breast tumour microenvironment at single-cell resolution. Oral presentation at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract GS1-01.