PMID- 37840200 OWN - NLM STAT- MEDLINE DCOM- 20240130 LR - 20240206 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 54 IP - 1 DP - 2024 Jan TI - Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry. PG - e2350616 LID - 10.1002/eji.202350616 [doi] AB - Dendritic cells (DCs) are essential in antitumor immunity. In humans, three main DC subsets are defined: two types of conventional DCs (cDC1s and cDC2s) and plasmacytoid DCs (pDCs). To study DC subsets in the tumor microenvironment (TME), it is important to correctly identify them in tumor tissues. Tumor-derived DCs are often analyzed in cell suspensions in which spatial information about DCs which can be important to determine their function within the TME is lost. Therefore, we developed the first standardized and optimized multiplex immunohistochemistry panel, simultaneously detecting cDC1s, cDC2s, and pDCs within their tissue context. We report on this panel's development, validation, and quantitative analysis. A multiplex immunohistochemistry panel consisting of CD1c, CD303, X-C motif chemokine receptor 1, CD14, CD19, a tumor marker, and DAPI was established. The ImmuNet machine learning pipeline was trained for the detection of DC subsets. The performance of ImmuNet was compared with conventional cell phenotyping software. Ultimately, frequencies of DC subsets within several tumors were defined. In conclusion, this panel provides a method to study cDC1s, cDC2s, and pDCs in the spatial context of the TME, which supports unraveling their specific roles in antitumor immunity. CI - (c) 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. FAU - van der Hoorn, Iris A E AU - van der Hoorn IAE AUID- ORCID: 0009-0008-8644-0678 AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Martynova, Evgenia AU - Martynova E AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, the Netherlands. FAU - Subtil, Beatriz AU - Subtil B AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Meek, Jelena AU - Meek J AUID- ORCID: 0000-0001-8439-282X AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Verrijp, Kiek AU - Verrijp K AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Textor, Johannes AU - Textor J AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Data Science, Institute for Computing and Information Sciences, Radboud University, Nijmegen, the Netherlands. FAU - Florez-Grau, Georgina AU - Florez-Grau G AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Piet, Berber AU - Piet B AD - Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - van den Heuvel, Michel M AU - van den Heuvel MM AD - Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - de Vries, I Jolanda M AU - de Vries IJM AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Gorris, Mark A J AU - Gorris MAJ AD - Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands. AD - Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Nijmegen, the Netherlands. LA - eng GR - Hanarth Fonds/ GR - Vi.Vidi.192.084/Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ GR - LSHM18056-SGF/Health~Holland/ PT - Journal Article DEP - 20231024 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Biomarkers, Tumor) SB - IM MH - Humans MH - *Tumor Microenvironment MH - Immunohistochemistry MH - Biomarkers, Tumor MH - *Neoplasms/metabolism MH - Dendritic Cells OTO - NOTNLM OT - DCs OT - Multiplex Immunohistochemistry OT - Tumor Microenvironment EDAT- 2023/10/16 06:48 MHDA- 2024/01/30 12:42 CRDT- 2023/10/16 00:13 PHST- 2023/10/12 00:00 [revised] PHST- 2023/06/19 00:00 [received] PHST- 2023/10/13 00:00 [accepted] PHST- 2024/01/30 12:42 [medline] PHST- 2023/10/16 06:48 [pubmed] PHST- 2023/10/16 00:13 [entrez] AID - 10.1002/eji.202350616 [doi] PST - ppublish SO - Eur J Immunol. 2024 Jan;54(1):e2350616. doi: 10.1002/eji.202350616. Epub 2023 Oct 24.