Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer

Abstract

There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.

Profiles of circulating fatty acids are population-specific and linked to prostate cancer

“…Men of African ancestry, including African American (AA) and Ghanaian men, have a disproportionately higher burden of lethal prostate cancer when compared to European American (EA) men 1,3 . This increased mortality burden could be partially attributed to unique risk factor pro les by population group, as well as distinct in ammatory and immune responses that drive cancer aggressiveness and impact survival, as we have shown 4 .…”

“…Association of clinical/socio-demographic characteristics with circulating fatty acids. In similar fashion to our previous proteomic study on these cohorts 4 , we assessed the associations of age, BMI, education, smoking, diabetes, and aspirin use with the abundance of individual circulating fatty acids (as continuous values) by means of multivariable linear regression models implemented by the function lm in the base R package stats (version 3.6.1). For each fatty acid, we tted the formula "fatty acid ~ age + bmi + education + smoking + diabetes + aspirin", which yielded the model's F-statistic and associated Fstatistic p value, as well as the intercept and regression coe cients with their associated standard errors (SE) and P values.…”

“…To assess if fatty acid levels were associated with disease severity, we correlated individual fatty acids and fatty acid classes with National Comprehensive Cancer Network (NCCN) risk scores that describe disease severity 16 , which were obtained for the AA and EA patients in the NCI-Maryland study 4 . In this analysis, only palmitoleic acid showed a positive dose-dependent relationship with increasing NCCN risk scores, even after adjusting for multiple testing (P trend = 0.002, Supplementary Table 15).…”

“…Circulating fatty acids may in uence the immune environment. For the NCI-Maryland and NCI-Ghana studies, 82 immune-oncological markers have previously been measured and grouped into pathways: apoptosis/cell killing, autophagy/metabolism, chemotaxis/tra cking to tumor, suppression of tumor immunity (Th2 response, tolerogenic), promotion of tumor immunity (Th1 responses), vasculature 4 . Thus, we assessed whether there was a relationship between the immune-oncology marker-de ned pathways and circulating fatty acid levels.…”

Association of Neighborhood Deprivation With Prostate Cancer and Immune Markers in African American and European American Men

“…A recent study by several authors of the present study reported that immune-oncology marker profiles differ between men of African and European descent, which was partly explained by ancestry. 24 To evaluate whether marker profiles influenced by the neighborhood environment, we examined potential associations with 6 serum proteomics-defined biological pathways based on measurement of these 82 immune-oncology markers. We restricted this examination to the control population to exclude a confounding effect of prostate cancer.…”