A research team has revealed a distinct molecular signature in the tumor tissues of Black patients with breast cancer. The new work, published by Yao et al in JNCI: Journal of the National Cancer Institute, reported that an elevated number of “exhausted,” nonfunctional T cells appears to lead to tumors in Black patients to be more aggressive and difficult to treat.
This finding may also open the door to treatment interventions that could help eliminate the disparities in survival between Black and White patients with breast cancer. In the United States, rates of death from breast cancer are 40% higher among Black women than White women.
Study Methods
Seeking new information about what is driving those unequal outcomes, the team—comprising researchers from Roswell Park Comprehensive Cancer Center—used both pathologic and gene-expression profiling to characterize infiltrating immune cells in the breast tumor microenvironment of 1,315 patients included in the Women’s Circle of Health Study.
Disparities Uncovered
The data the team compiled revealed distinct differences in the tumor immune responses among Black and White patients. While tumors from Black patients exhibited a stronger overall immune cell presence, the immune cells in Black patients appeared to have lower antitumor activities.
“We observed in the tumor microenvironment of breast cancer in [Black] patients a distinct signature of exhausted vs total CD8-positive T cells, and noted further that this immune cell profile is associated with poorer breast cancer survival, particularly in the hormone receptor–positive subtype of breast cancer,” said first study author Song Yao, PhD, Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park.
KEY POINTS
- While tumors from Black patients exhibited a stronger overall immune cell presence, the immune cells in Black patients appeared to have lower antitumor activities.
- Researchers noted that they found the tumor microenvironment of breast cancer in [Black] patients had a distinct signature of exhausted vs total CD8-positive T cells, and noted further that this immune cell profile is associated with poorer breast cancer survival, particularly in the hormone receptor–positive subtype of breast cancer.
The findings suggest that Black patients could have a higher response rate to immune checkpoint inhibitors. The potential of this approach is also supported, the authors noted, by the stronger B-cell response in this patient population, a trait recently shown to regulate responses to immunotherapy.
“The activation of the immune system to eliminate and control cancer cells has become a clinical reality with recent breakthroughs in cancer immunotherapy,” noted senior study author Christine B. Ambrosone, PhD, Chair of Cancer Prevention & Control and Senior Vice President of Population Sciences at Roswell Park. “We believe these findings may suggest an opportunity to enlist host immunity, part of the fundamental mechanism of human bodies to recognize and defend against the invasion of foreign agents, through immune checkpoint inhibitors in patients whose breast cancers fit this immune profile.”
The team also highlighted a lack of clinical trials on immune checkpoint inhibitors that have reported race-specific outcome data, emphasizing the need for enhanced recruitment of racial/ethnic minorities to lessen cancer disparities.
Disclosure: The study was partially supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit academic.oup.com.
