MCW Scientists Discover Chemokine Levels May Contribute to Prostate Cancer Disparities

African American contemplatingWhile progress has been made in various methods of cancer prevention, diagnosis, and treatment over the last few decades, certain populations continue to face disparities. Prostate cancer is one such disease that disproportionately affects African American (AA) men, who currently experience a higher incidence and twice the mortality rate compared to white men. Findings from a new MCW study offer hope for bridging these gaps, revealing that biological factors, like chemokine levels, may explain racial disparities in prostate cancer lethality. Investigators say the results, recently published in Cancer, could help guide therapeutic approaches to improve prostate cancer outcomes in AA men.

“We discovered that elevated serum levels of chemokines CXCL5 and CXCL2, coupled with low levels of CCL23, may contribute to suppressed antitumor immunity and explain the aggressive nature of prostate cancer in AA men. Patient age, prostate‐specific antigen, or Gleason scores were not significantly associated with these chemokines,” said Dev Karan, PhD, associate professor, Pathology & Laboratory Medicine, and first author of the study. “Although socioeconomic factors may be blamed to a certain extent, we recognize that the differences in tumor biology make AA men more prone to aggressive prostate cancer.”

“The observed disproportionate level of serum chemokines may help guide therapeutic approaches and open avenues for targeted treatments, such as antibody-directed neutralization of the identified chemokines, to improve prostate cancer outcomes in AA men,” added Dr. Karan.

Chemokines are cell‐secreted proteins with diverse physiological functions, including leukocyte trafficking, angiogenesis, inflammation, tumorigenesis, and metastasis. To improve their understanding of the biological differences between AA and white men, the research team analyzed serum levels of various chemokines and cytokines from preoperative prostate cancer patients. Their findings shed light on three chemokines:

  • CXCL5 is known for its role in promoting cancer progression and metastasis, impairing immune cell function. It showed increased serum levels in AA men.
  • CXCL2, whose role in cancer progression is less characterized, potentially contributes to a compromised immune response against prostate cancer. It also showed increased serum levels in AA men.
  • CCL23 displayed race- and cancer-specific differences with significantly higher serum levels in white men. While the role of CCL23 in cancer suppression is not fully understood, its elevation in other cancers has been linked to positive outcomes.

Cancer disparities represent a significant public health concern in the United States and across the world. By investigating the factors that contribute to differences in cancer outcomes among diverse populations, scientists can uncover new insights into the complex interplay of genetic, environmental, and social factors that influence cancer risk and progression. Dr. Karan said he is excited to advance this work and discover more ways to improve outcomes for all patients with prostate cancer.

“We look forward to investigating the mechanism on the biological impact of the identified chemokines in regulating the immunobiology of prostate cancer, and their role in contributing to disparities. In addition, validating an antibody‐directed neutralization of such chemokines in preclinical models may have the translational potential of such an approach and improve equitability in precision oncology to benefit prostate cancer patients,” said Dr. Karan.

Read the full study in Cancer.