Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Front Immunol. 2024 Jan 22:14:1307873. doi: 10.3389/fimmu.2023.1307873. eCollection 2023.

Abstract

Background: For patients with high grade serous carcinoma of the ovary (HGSC), survival rates have remained static for the last half century. Despite the presence of tumor mutations and infiltration of immune cells, existing immunotherapies have achieved little success against HGSC. These observations highlight a gap in the understanding of how the immune system functions and interacts within HGSC tumors.

Methods: We analyzed duplicate core samples from 939 patients with HGSC to understand patterns of immune cell infiltration, localization, and associations with clinical features. We used high-parameter immunohistochemical/Opal multiplex, digital pathology, computational biology, and multivariate analysis to identify immune cell subsets and their associations with HGSC tumors.

Results: We defined six patterns of cellular infiltration by spatially restricted unsupervised clustering of cell subsets. Each pattern was represented to some extent in most patient samples, but their specific distributions differed. Overall (OS) and progression-free survival (PFS) corresponded with higher infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.

Conclusions: Immune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment.

Keywords: CD16A; high grade serous cancer; natural killer (NK) cell; ovarian cancer; spatial biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cystadenocarcinoma, Serous* / drug therapy
  • Cystadenocarcinoma, Serous* / genetics
  • Cystadenocarcinoma, Serous* / pathology
  • Female
  • Humans
  • Killer Cells, Natural / pathology
  • Macrophages / pathology
  • Ovarian Neoplasms* / genetics
  • T-Lymphocytes / pathology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study uses resources provided by the Canadian Ovarian Cancer Research Consortium’s COEUR biobank, which was funded by the Terry Fox Research Institute and Ovarian Cancer Canada, and maintained and supervised at the Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM). BHN receives support from BC Cancer Foundation, Terry Fox Research Institute, and Canadian Institutes of Health Research. This work was supported by a New Investigator award to JB through theTerry Fox ImmunoTherapeutic NeTwork (iTNT) (Grant #1086) and the Ovarian Cancer Expert Alliance of Nova Scotia (OCEANS) network with support from Ovarian Cancer Canada and the Government of Nova Scotia. SN, SL, JM and RA are trainees in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute; funds for RA and JM are provided by GIVETOLIVE. SN is supported by a Dalhousie University President’s award, Killam pre-doctoral award, a Nova Scotia Graduate Scholarship, and a Vanier Canada Graduate Scholarship through the Canadian Institutes of Health Research. SL is supported by a CIHR CGS-D award and a Nova Scotia Graduate Scholarship. RA and JM are supported by the Kilpatrick Trust through the Dalhousie Faculty of Medicine 2023 Graduate Studentship program.