The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas-Reference-Cited by-同舟云学术

The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Published:2023-06-20 Issue:17 Volume:29 Page:3471-3483
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Heinze Karolin¹²^ORCID,Cairns Evan S.¹^ORCID,Thornton Shelby²³^ORCID,Harris Bronwyn³^ORCID,Milne Katy³^ORCID,Grube Marcel⁴^ORCID,Meyer Charlotte²⁴^ORCID,Karnezis Anthony N.⁵^ORCID,Fereday Sian⁶⁷^ORCID,Garsed Dale W.⁶⁷^ORCID,Leung Samuel C.Y.²^ORCID,Chiu Derek S.²^ORCID,Moubarak Malak⁸^ORCID,Harter Philipp⁸^ORCID,Heitz Florian⁸⁹^ORCID,McAlpine Jessica N.¹²^ORCID,DeFazio Anna¹⁰¹¹¹²¹³^ORCID,Bowtell David D.L.⁶⁷^ORCID,Goode Ellen L.¹⁴^ORCID,Pike Malcolm¹⁵^ORCID,Ramus Susan J.¹⁶¹⁷^ORCID,Pearce C. Leigh¹⁷¹⁸^ORCID,Staebler Annette¹⁹^ORCID,Köbel Martin²⁰^ORCID,Kommoss Stefan⁴^ORCID,Talhouk Aline¹²^ORCID,Nelson Brad H.²³¹⁷^ORCID,Anglesio Michael S.¹²^ORCID

Affiliation:

1. 1Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.

2. 2OVCARE - British Columbia's Gynecological Cancer Research Program, BC Cancer, Vancouver General Hospital, and the University of British Columbia, Vancouver, British Columbia, Canada.

3. 3Molecular and Cellular Immunology Core (MCIC), Deeley Research Centre, BC Cancer, Victoria, Canada.

4. 4Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.

5. 5Department of Pathology and Laboratory, UC Davis Medical Center, Sacramento, California.

6. 6Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

7. 7Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

8. 8Kliniken Essen Mitte, Department of Gynecology and Gynecologic Oncology, Essen, Germany.

9. 9Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

10. 10Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.

11. 11Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.

12. 12Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

13. 13The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia.

14. 14Mayo Clinic, Department of Health Science Research, Division of Epidemiology, Rochester, Minnesota.

15. 15Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

16. 16School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales Sydney, Sydney, Australia.

17. 17Multidisciplinary Ovarian Cancer Outcomes Group (Consortium).

18. 18School of Public Health, University of Michigan, Ann Arbor, Michigan.

19. 19Institute of Pathology, University Hospital of Tübingen, Tübingen, Germany.

20. 20Department of Pathology, University of Calgary, Calgary, Alberta, Canada.

Abstract

Abstract Purpose: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. Experimental Design: We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. Results: Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1–14.7; P < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. Conclusions: Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.

Funder

Deutsche Forschungsgemeinschaft

Janet D. Cottrelle Foundation

Michael Smith Health Research BC

BC Cancer Foundation

VGH and UBC Hospital Foundation

National Health and Medical Research Council

National Cancer Institute

U.S. Army Medical Research and Development Command

Victorian Cancer Agency

Publisher

American Association for Cancer Research (AACR)