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William J. Gradishar, MD, FACP, FASCO


Can Macrophages Improve Patient Outcome in Breast Cancer Better Than T Cells?

By: Victoria Kuhr, BA
Posted: Friday, May 19, 2023

Dario Vignali, PhD, and Steffi Oesterreich, PhD, of the University of Pittsburgh School of Medicine, and colleagues proposed that macrophages, not T cells, are the predominant immune cells infiltrating the tumor bed of invasive ductal carcinoma and invasive lobular carcinoma. Macrophages are also the most transcriptionally diverse cell subset between invasive ductal carcinoma and invasive lobular carcinoma. Additionally, the good “cellular neighborhoods” between macrophages and T cells appeared to be associated with longer disease-free survival in invasive ductal carcinoma and not invasive lobular carcinoma. These findings were published in Nature Cancer.

“These findings tell us that zooming out to look at the architecture of the tumor and understanding how immune cells influence each other, rather than simply looking at overall quantities of cells, is important,” said first author Sayali Onkar, PhD, in a University of Pittsburgh press release. Dr. Onkar was a graduate student at the University of Pittsburgh School of Medicine during this research and is currently at Mount Sinai Icahn School of Medicine, New York. “Targeting cellular neighborhoods within the tumor microenvironment could have a meaningful impact on patient outcomes.”

The study included postoperative treatment-naive fresh tumors as well as matched tumor-adjacent and peripheral blood samples from individuals diagnosed with invasive ductal carcinoma and invasive lobular carcinoma. Samples were compared with nontumor breast reduction mammoplasty tissues. The study authors conducted phenotypic, transcriptional, and functional analyses for a cohort of treatment-naive invasive ductal carcinoma and invasive lobular carcinoma tumors.

A total of 94 invasive ductal carcinoma and 87 invasive lobular carcinoma tumors were evaluated in the study. Overall, 69% of all estrogen receptor–positive tumors (37 of 53) increased immune cells of significantly higher infiltration of B cells, CD4-positive T conventional cells, CD8-positive T cells, and regulatory T cells than tumor-adjacent tissues. This significance was driven by the invasive ductal carcinoma subset and not the invasive lobular carcinoma subset, as revealed by subtype-specific paired tumor-adjacent and tumor tissue analysis. In invasive ductal carcinoma, one type of neighborhood dominated by macrophages and CD8-positive T cells appears to be associated with increased disease-free survival in patients. This finding suggest that these immune cells work together to kill cancer cells. Additionally, invasive lobular carcinoma samples had more tumor-promoting M2-like macrophages and fewer tumor-fighting M1-like macrophages than invasive ductal carcinoma samples.

Disclosure: For full disclosures of the study authors, visit

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