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Abundance of plasma cells tied to better outcomes in Blacks with prostate cancer

Nature Communications
Reuters Health - 16/02/2021 - Prostate tumors in Black men and men of African ancestry have an increased proportion of plasma cell infiltrates, which correlate with improved outcomes after surgery, researchers say.

Reports in the literature suggest that prostate cancers in these men are more responsive to immune-based treatments, Dr. Edward Schaeffer of Northwester University Feinberg School of Medicine in Chicago told Reuters Health by email. "Our study found that Black men and men of African ancestry did in fact have more immune cells infiltrating their cancers. Specifically, we found enhanced plasma cells as measured by the commercially available molecular testing platform, Decipher."

"Bioinformatic analysis further demonstrated that men with enhanced plasma cell and tertiary lymphoid structures had improved metastasis-free and cancer-specific survival," he said.

As reported in Nature Communications, the team used transcriptional profiling from prostate cancer cohorts enriched with samples from Black men or men of African ancestry to assess the tumor microenvironment immune infiltrate of these men.

They evaluated 1,300 samples from three prostate cancer patient cohorts, including 452 from Black men and 58 from men of African ancestry.

The Black men and men of African ancestry had more infiltrating lymphocytes, and the researchers hypothesized that this may be due to an increase in plasma cells and augmented interferon gamma signaling, IgG expression, and NK activity.

As Dr. Schaeffer noted, they also found an increase in plasma cell content, which is associated with increased immune activity and could be associated with prolonged recurrence-free survival following prostate cancer surgery.

Further analysis suggested that the findings are not unique to Blacks and that elevated plasma cell levels were associated with improved post-surgical recurrence-free survival.

Summing up, the authors state, "These findings suggest that plasma cells could be potential biomarkers or targets for therapeutic response to immunotherapy for use in future prospective evaluation. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness."

Dr. Schaeffer said, "We are developing clinical trials that will test if these men do in fact have augmented response to immunotherapies with the hope that our observations will extend to many men with locally advanced and metastatic prostate cancer. Clinicians interested in this concept can explore it through the Decipher Test and their genomic resource call the GRID."

Dr. Robert Uzzo, Chairman, Department of Surgery at Fox Chase Cancer Center in Philadelphia, commented by email to Reuters Health, "The findings are provocative, as they suggest a potentially different immunological response to prostate cancer than other solid tumors."

"In most cancer, the increased lymphocytes that have been observed are of the T cell lineage, whereby cancer cell death is mediated directly through the interaction of T cells and cancer cells," he noted. "Augmenting this response is the basis for most current immunotherapies."

"If these findings are to have clinical significance, they suggest that the B cell response is an important mediator of anti-tumor immunity in some men with prostate cancer," he said. "If true, this could have significant therapeutic implications, as a rapidly emerging anti-cancer immune therapeutic category includes the use of engineered bispecific antibodies... to augment the T cell response and/or deliver a cytotoxic drug conjugate. These and other drugs exploiting antibody platforms are in the clinical trials pipeline for men with advanced prostate cancer."

"Data like those presented in this paper are foundational to next generation immunotherapies for prostate cancer," he added.

SOURCE: https://go.nature.com/3jThcpo Nature Communications, online February 10, 2021.

By Marilynn Larkin

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