Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

S T Paijens; A Vledder; D Loiero; E W Duiker; J Bart; A M Hendriks; M Jalving; H H Workel; H Hollema; N Werner; A Plat; G B A Wisman; R Yigit; H Arts; A J Kruse; N M de Lange; V H Koelzer; M de Bruyn; H W Nijman

doi:10.1080/2162402X.2021.1935104

Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

Oncoimmunology. 2021 Jun 6;10(1):1935104. doi: 10.1080/2162402X.2021.1935104.

Authors

S T Paijens¹, A Vledder¹, D Loiero², E W Duiker³, J Bart³, A M Hendriks⁴, M Jalving⁴, H H Workel¹, H Hollema³, N Werner³, A Plat¹, G B A Wisman¹, R Yigit¹, H Arts¹, A J Kruse⁵, N M de Lange⁵, V H Koelzer², M de Bruyn¹, H W Nijman¹

Affiliations

¹ Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
² Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland.
³ Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ Department of Obstetrics and Gynecology, Isala Hospital Zwolle, Zwolle, The Netherlands.

Abstract

CD103-positive tissue resident memory-like CD8⁺ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

Keywords: CD8CD103 t cell; digital quantification; high grade serous ovarian cancer; overall survival; prognosis; tissue resident memory t cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Cystadenocarcinoma, Serous*
Female
Humans
Lymphocytes, Tumor-Infiltrating
Ovarian Neoplasms*
Prognosis
T-Lymphocyte Subsets

Grants and funding

The study is supported by the Dutch Cancer Society: project grant RUG 2015-7235.