Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Maartje C. A. Wouters, Fenne L. Komdeur, Hagma H. Workel, Harry G. Klip, Annechien Plat, Neeltje M. Kooi, G. Bea A. Wisman, Marian J. E. Mourits, Henriette J. G. Arts, Maaike H. M. Oonk, Refika Yigit, Steven de Jong, Cornelis J. M. Melief, Harry Hollema, Evelien W. Duiker, Toos Daemen, Marco de Bruyn, Hans W. Nijman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)

Abstract

Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.

Experimental Design: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence.

Results: A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (

Conclusions: Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. (C) 2015 AACR.

Original languageEnglish
Pages (from-to)714-724
Number of pages11
JournalClinical Cancer Research
Volume22
Issue number3
DOIs
Publication statusPublished - 1-Feb-2016

Keywords

  • NEGATIVE BREAST-CANCER
  • NEOADJUVANT CHEMOTHERAPY
  • MONOCLONAL-ANTIBODY
  • IN-VIVO
  • SURVIVAL
  • SURGERY
  • IMMUNOTHERAPY
  • RESPONSES
  • EFFECTOR

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