Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa-Reference-Cited by-同舟云学术

Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa

Published:2023-04-14 Issue:6 Volume:11 Page:720-731
ISSN:2326-6066
Container-title:Cancer Immunology Research
language:en
Short-container-title:

Author:

Bauer Marcus¹²^ORCID,Vetter Martina³^ORCID,Stückrath Kathrin³^ORCID,Yohannes Meron⁴^ORCID,Desalegn Zelalem⁵^ORCID,Yalew Tewodros⁶^ORCID,Bekuretsion Yonas⁶^ORCID,Kenea Tariku W.⁷^ORCID,Joffe Maureen⁸⁹¹⁰^ORCID,van den Berg Eunice J.¹¹^ORCID,Nikulu Julien I.¹²,Bakarou Kamate¹³^ORCID,Manraj Shyam S.¹⁴^ORCID,Ogunbiyi Olufemi J.¹⁵^ORCID,Ekanem Ima-Obong¹⁶^ORCID,Igbinoba Festus¹⁷^ORCID,Diomande Mohenou¹⁸^ORCID,Adebamowo Clement¹⁹^ORCID,Dzamalala Charles P.²⁰^ORCID,Anele Angelica A.²¹^ORCID,Zietsman Annelle²²^ORCID,Galukande Moses²³^ORCID,Foerster Milena²⁴^ORCID,dos-Santos-Silva Isabel²⁵^ORCID,Liu Biying²⁶^ORCID,Santos Pablo²^ORCID,Jemal Ahmedin²⁷^ORCID,Abebe Tamrat⁴^ORCID,Wickenhauser Claudia¹^ORCID,Seliger Barbara²⁸²⁹³⁰^ORCID,McCormack Valerie²⁴^ORCID,Kantelhardt Eva J.²³^ORCID

Affiliation:

1. 1Department of Pathology, University Hospital Halle, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

2. 2Global Health Working Group, Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

3. 3Department of Gynecology, University Hospital Halle, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

4. 4Department of Medical Laboratory Science, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

5. 5Department of Microbiology, Immunology & Parasitology, School of Medicine, College of Health Sciences, Tikur Anbessa Specialized Hospital, Addis Ababa University, Addis Ababa, Ethiopia.

6. 6Department of Pathology, Tikur Anbessa Specialized University Hospital, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

7. 7Department of Surgery, Aira General Hospital, Aira, Ethiopia.

8. 8Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa.

9. 9Strengthening Oncology Services Research Unit, Faculty of Health Sciences, Univeristy of Witwatersrand, Johannesburg, South Africa.

10. 10SAMRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

11. 11Department of Anatomical Pathology, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa.

12. 12Ligue Congolaise Contre le Cancer, l'Unité Pilote du GFAOP, Lubumbashi, Democratic Republic of the Congo.

13. 13Service d'Anatomie, Cytologie Pathologique au C.H.U. du point G, BP 333, Bamako, Mali.

14. 14Central Health Laboratory, Victoria Hospital, Candos, Mauritius.

15. 15Department of Pathology, University College Hospital, Ibadan, Nigeria.

16. 16Department of Pathology, Calabar Cancer Registry, University of Calabar Teaching Hospital, Calabar, Nigeria.

17. 17National Hospital, Abuja, Nigeria.

18. 18Service d'Anatomie et Cytologie Pathologiques, Abidjan, Côte d'Ivoire.

19. 19Department of Epidemiology and Public Health, and the Marlene and Stewart Greenebaum, Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland.

20. 20Department of Pathology, Malawi College of Medicine, Blantyre, Malawi.

21. 21Federal Medical Centre, Owerri, Nigeria.

22. 22AB May Cancer Centre, Windhoek Central Hospital, Windhoek, Namibia.

23. 23College of Health Sciences, Makerere University, Kampala, Uganda.

24. 24International Agency for Research on Cancer (IARC/WHO), Environment and Lifestyle Epidemiology Branch, Lyon, France.

25. 25Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom

26. 26African Cancer Registry Network, Oxford, United Kingdom.

27. 27Surveillance and Health Equity Science, American Cancer Society, Atlanta, Georgia.

28. 28Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

29. 29Institute of Translational Immunology, Medical School Theodor Fontane, Brandenburg an der Havel, Germany.

30. 30Fraunhofer Institute for Immunology, Leipzig, Germany.

Abstract

Abstract The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients’ prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the “African Breast Cancer-Disparities in Outcomes (ABC-DO) Study,” were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705

Funder

Else Kröner-Fresenius-Stiftung

Susan G. Komen North Carolina

Susan G. Komen

Deutsche Krebshilfe

German Academic Exchange Service New Delhi

Center for Strategic Scientific Initiatives, National Cancer Institute

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Immunology

Link