BETHESDA, MD — Better understanding of the cellular immune components underlying aggressive prostate cancer, especially among African American (AA) men who are disproportionately affected by the disease compared with white men, could help improve precision medicine treatment strategies, according to a new study.
The research was conducted by the Murtha Cancer Center Research Program, the Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, all in Bethesda, MD, as well as other groups.
“We aimed to evaluate which immune-related genes and cell types are differentially expressed in AA tumors and how immunobiology impacts prostate cancer progression,” the researchers wrote in Cancer Research Communications.1
To do that, the study team purified nucleic acid from tumor biopsies, which were obtained following radical prostatectomy in 51 patients—26 African American and 25 Caucasian.
The gene expression was measured using the NanoString platform, and researchers estimated immune cell abundances and assessed differences between groups based on clinicopathologic data. “Product-limit estimates determined associations with biochemical recurrence (BCR)-free and metastasis-free survival,” they wrote.
Results indicated that DVL2 and KLRC2 were significantly upregulated in CA tumors and were associated with worse disease progression. No significant differences in immune cell abundances by race were observed, however.
On the other hand, the study team reported, “Highly significant reductions in abundances of mast cells versus tumor-infiltrating lymphocytes (TIL) were found in men with high-grade pathologies and in men who later developed metastases.”
The study pointed out that low ratios of mast cells versus TILs were associated with worse BCR-free survival and metastasis-free survival, adding, “Although estimated immune cell abundances were not different by race, we identified genes involved in metabolism and natural killer cell functions that were differentially expressed between AA and CA tumors. Among the entire cohort, depletion of mast cells within prostatectomy tumors was characteristic of advanced disease and susceptibility to disease progression.”
The researchers said their findings “demonstrate that there are immune-related genes and pathways that differ by race. Impaired intratumoral cellular immune composition, especially for TIL-normalized mast cells, may be vital in predicting and contributing to prostate cancer disease progression.”
Background information in the study advised that “equitable access to care and other social determinants of health are known factors impacting prostate cancer disparity, yet even when these factors are accounted for, the exact biologic, epigenetic and immunologic molecular mechanisms that may contribute to these differential incidences and outcomes for AA men are still not completely understood.”
One reason, according to the researchers, is the limited availability of tumor specimens from AA men in those studies. “Mindful of these considerations, we aimed to use specimens from men with equal access to health care in the Military Health System (MHS) to evaluate whether racial differences exist in the immunobiology of prostate cancer, especially among young AA men, and whether any immune cell profiles or specific immune-related genes are associated with disease progression,” they wrote.
- Schafer CC, Jiang J, Elsamanoudi S, Nousome D, et. al. Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression. Cancer Res Commun. 2023 Aug 1;3(8):1423-1434. doi: 10.1158/2767-9764.CRC-22-0463. PMID: 37534375; PMCID: PMC10392708.