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BCRF-Supported Study Shows Distinct Differences in Black Women’s Immune Response

Research among the first to investigate immune cells in breast tumor microenvironments by race

A new study from BCRF investigators Drs. Christine Ambrosone and Chi-Chen Hong of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. is the first to extensively profile distinct differences between the immune cells in Black and white women’s breast tumor microenvironments.

Numerous studies have been dedicated to researching and understanding the breast tumor microenvironment—the ecosystem of the vessels, cells, molecules, and support structures surrounding a malignancy—and its influence on tumor growth, metastasis, and more. This research has accelerated in recent years especially as gene expression profiling and single cell analyses have become more accessible. However, there has been a notable lack of information regarding differences in the immune landscape of breast tumors by race and what role this may play in the mortality gap among Black women.

Black women are more frequently diagnosed at younger ages and later stages of the disease and with aggressive breast cancer subtypes (such as triple-negative) compared to women of other races. Devastatingly, they are 40 percent more likely to die from breast cancer, despite being diagnosed at similar rates as white women. 

More than a decade of research has suggested that biology may play a role in how Black women are affected by breast cancer. Continuing to research biological differences is paramount to reducing the disparities this group faces in survival outcomes.

Drs. Ambrosone and Hong’s new research represents an important step toward uncovering differences in the tumor microenvironments of breast cancer in Black women and shining a light on what’s driving these unequal outcomes—and why more research is critical.

How T Cells Fight Cancer—and How Cancer Fights Back

The immune system—the body’s natural defense—is a complex network of players that work together to fight off threats, including cancer. One key cell type, designated as CD8+ T cells, are capable of recognizing and killing cancer cells.

Some cancer cells, however, can protect themselves from T cells by targeting immune checkpoints, key regulators of the immune system that, when activated, dampen the immune response. Using this strategy, the cancer can effectively evade immune attack and grow unchecked.

What BCRF investigators found

Drs. Ambrosone and Hong profiled the immune tumor microenvironments surrounding breast tumors in 1,315 people from the Women’s Circle of Health Study, which specifically aims to investigate racial disparities in breast cancer. They found a marked difference in the composition and cell-killing capacity of immune cells surrounding the breast tumors between Black and white women regardless of their breast cancer subtypes.

Black women with breast cancer had a stronger overall immune response but more exhausted CD8+ T cells, which are less responsive and less able to effectively fight the tumor. Patients who had higher ratios of exhausted CD8+ T cells to total CD8+ T cells consistently had worse outcomes. This distinct immune signature among Black women may indicate an immunological factor contributing to more aggressive breast cancer.

The significance of this finding—and a need for more research

The exhausted CD8+ T cell signature in Black women with breast cancer may present a unique opportunity for treatment with immunotherapy. Immune checkpoint inhibitors work by blocking immune checkpoints and preventing cancer cells from activating them, thereby restoring immune function. This strategy has been successful in treating many cancer types, including triple-negative breast cancer, which disproportionately affects young Black women and BRCA1 mutation carriers. If CD8+ T cell exhaustion is indeed causing disease progression in Black women with breast cancer, checkpoint inhibitors that activate CD8+ T cells could hold promise as a treatment. Reactivated CD8+ T cells, combined with a stronger immune response of other immune cell types (as observed in this group), could kickstart a Black woman's immune system to attack her cancer more vigorously and improve her outcome.

The results of this study highlight the need to accrue sufficient numbers of racial and ethnic minorities into clinical trials and to report race-specific outcomes data. Differences in drug response by race, for example, will not be detectable if there is not an adequate population participating in a trial. Enhanced recruitment of minority populations will ultimately lead to new insights like this one, lessen breast cancer disparities, and ensure that all patients have the opportunity to benefit from cutting-edge cancer treatments.

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