Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy

Beatris Mastelic-Gavillet; Apostolos Sarivalasis; Leyder Elena Lozano; Sebastien Lofek; Tania Wyss; Ignacio Melero; I Jolanda M de Vries; Alexandre Harari; Pedro Romero; Lana Elias Kandalaft; Selena Viganó

doi:10.3389/fimmu.2023.1119371

Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy

Front Immunol. 2023 Feb 10:14:1119371. doi: 10.3389/fimmu.2023.1119371. eCollection 2023.

Authors

Beatris Mastelic-Gavillet^{1

2}, Apostolos Sarivalasis¹, Leyder Elena Lozano^{1

2}, Sebastien Lofek^{1

2}, Tania Wyss^{1

2

3}, Ignacio Melero^{4

5

6

7}, I Jolanda M de Vries⁸, Alexandre Harari^{1

2}, Pedro Romero^{1

2}, Lana Elias Kandalaft^{1

2}, Selena Viganó^{1

2}

Affiliations

¹ Department of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, Switzerland.
² Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
³ Bioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
⁴ Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
⁵ Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain.
⁶ Departments of Immunology-Immunotherapy and Oncology, University Clinic, University of Navarra, Pamplona, Spain.
⁷ Program of Immunology and Immunotherapy, Centro de Investigacion Biomedica en Red Cancer, Madrid, Spain.
⁸ Department of Tumour Immunology, Radboud Institute of Molecular Life Sciences, Nijmegen, Netherlands.

Abstract

Background: The use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced.

Methods: We recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry.

Results: We show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141⁺ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased.

Conclusions: Our study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.

Keywords: DC; TLR3; cancer vaccine; chemotherapy; ovarian cancer.

Publication types

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

MeSH terms

Dendritic Cells* / immunology
Female
Humans
Immunotherapy
Monocytes
Neoplasm Recurrence, Local*
Ovarian Neoplasms* / drug therapy

Grants and funding

The European Community’s Horizon 2020 (EU grant PROCROP, no 635,122).