PMID- 32590296 OWN - NLM STAT- MEDLINE DCOM- 20201230 LR - 20211204 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 135 DP - 2020 Aug TI - Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer. PG - 173-182 LID - S0959-8049(20)30240-9 [pii] LID - 10.1016/j.ejca.2020.04.036 [doi] AB - BACKGROUND: Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141(bright)), cDC2s (CD1c(+)) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC). PATIENTS AND METHODS: Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets. RESULTS: In both patient groups, the frequency of total CD141(+) DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141(+) DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival. CONCLUSIONS: cDC1s are reduced in patients with OvC, and CD141(+) DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141(+) DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Mastelic-Gavillet, Beatris AU - Mastelic-Gavillet B AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. FAU - Sarivalasis, Apostolos AU - Sarivalasis A AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. FAU - Lozano, Leyder Elena AU - Lozano LE AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. FAU - Wyss, Tania AU - Wyss T AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland; Bioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. FAU - Inoges, Susana AU - Inoges S AD - Division of Immunology and Immunotherapy, Center for Applied Medical Researckh, University of Navarra, Pamplona, Spain; Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain; University Clinic, University of Navarra, Pamplona, Spain; Centro de Investigacion Biomedica en Red Cancer, Madrid, Spain. FAU - de Vries, Ingrid Jolanda Monique AU - de Vries IJM AD - Department of Tumour Immunology, Radboud Institute of Molecular Life Sciences, Geert Grooteplein 26-28, 6525 GA, Nijmegen, the Netherlands; Department of Medical Oncology, Radboudumc, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, the Netherlands. FAU - Dartiguenave, Florence AU - Dartiguenave F AD - Urology Research Unit, Department of Urology, CHUV, Switzerland. FAU - Jichlinski, Patrice AU - Jichlinski P AD - Urology Research Unit, Department of Urology, CHUV, Switzerland. FAU - Derre, Laurent AU - Derre L AD - Urology Research Unit, Department of Urology, CHUV, Switzerland. FAU - Coukos, George AU - Coukos G AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. FAU - Melero, Ignacio AU - Melero I AD - Division of Immunology and Immunotherapy, Center for Applied Medical Researckh, University of Navarra, Pamplona, Spain; Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain; University Clinic, University of Navarra, Pamplona, Spain; Centro de Investigacion Biomedica en Red Cancer, Madrid, Spain. FAU - Harari, Alexandre AU - Harari A AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. FAU - Romero, Pedro AU - Romero P AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. FAU - Vigano, Selena AU - Vigano S AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. Electronic address: selena.vigano@chuv.ch. FAU - Kandalaft, Lana Elias AU - Kandalaft LE AD - Department of Oncology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. Electronic address: lana.kandalaft@chuv.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200623 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antigens, Surface) RN - 0 (CA-125 Antigen) RN - 0 (CLEC9a protein, human) RN - 0 (Lectins, C-Type) RN - 0 (MUC16 protein, human) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Mitogen) RN - 0 (THBD protein, human) RN - 0 (TLR3 protein, human) RN - 0 (Thrombomodulin) RN - 0 (Toll-Like Receptor 3) RN - O84C90HH2L (Poly I-C) SB - IM MH - Aged MH - Aged, 80 and over MH - Antigens, Surface/blood MH - CA-125 Antigen/blood MH - Case-Control Studies MH - Dendritic Cells/drug effects/*immunology MH - Female MH - Flow Cytometry MH - Humans MH - Immunophenotyping MH - Lectins, C-Type/analysis MH - Male MH - Membrane Proteins/blood MH - Middle Aged MH - Ovarian Neoplasms/blood/*immunology/mortality MH - Phenotype MH - Poly I-C/pharmacology MH - Prognosis MH - Prostatic Neoplasms/blood/*immunology/mortality MH - Receptors, Mitogen/analysis MH - Thrombomodulin MH - Toll-Like Receptor 3/agonists OTO - NOTNLM OT - CD141 OT - Cross-presenting DC OT - Ovarian cancer OT - Prostate cancer OT - Vaccines OT - cDC1 COIS- Conflict of interest statement None declared. EDAT- 2020/06/27 06:00 MHDA- 2020/12/31 06:00 CRDT- 2020/06/27 06:00 PHST- 2020/03/20 00:00 [received] PHST- 2020/04/16 00:00 [accepted] PHST- 2020/06/27 06:00 [pubmed] PHST- 2020/12/31 06:00 [medline] PHST- 2020/06/27 06:00 [entrez] AID - S0959-8049(20)30240-9 [pii] AID - 10.1016/j.ejca.2020.04.036 [doi] PST - ppublish SO - Eur J Cancer. 2020 Aug;135:173-182. doi: 10.1016/j.ejca.2020.04.036. Epub 2020 Jun 23.