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

By FYH News Team

Published on April 4, 2022

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doi: 10.1038/s41467-022-29235-2.

Tsion Zewdu Minas^#¹, Julián Candia^#^{1

2}, Tiffany H Dorsey¹, Francine Baker¹, Wei Tang¹, Maeve Kiely¹, Cheryl J Smith¹, Amy L Zhang¹, Symone V Jordan¹, Obadi M Obadi¹, Anuoluwapo Ajao¹, Yao Tettey³, Richard B Biritwum³, Andrew A Adjei³, James E Mensah³, Robert N Hoover⁴, Frank J Jenkins⁵, Rick Kittles⁶, Ann W Hsing^{7

8}, Xin W Wang^{1

9}, Christopher A Loffredo¹⁰, Clayton Yates¹¹, Michael B Cook⁴, Stefan Ambs¹²

Affiliations

¹ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
² Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
³ University of Ghana Medical School, Accra, Ghana.
⁴ Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Division of Health Equities, Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁷ Stanford Cancer Institute, Stanford School of Medicine, Palo Alto, CA, USA.
⁸ Stanford Prevention Research Center, Stanford School of Medicine, Palo Alto, CA, USA.
⁹ Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
¹¹ Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
¹² Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ambss@mail.nih.gov.

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Tsion Zewdu Minas et al.

Nat Commun.

2022.

doi: 10.1038/s41467-022-29235-2.

Authors

Affiliations

¹ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
² Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
³ University of Ghana Medical School, Accra, Ghana.
⁴ Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Division of Health Equities, Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁷ Stanford Cancer Institute, Stanford School of Medicine, Palo Alto, CA, USA.
⁸ Stanford Prevention Research Center, Stanford School of Medicine, Palo Alto, CA, USA.
⁹ Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
¹¹ Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
¹² Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ambss@mail.nih.gov.

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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.

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