Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry

Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry

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....

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Published in:European journal of immunology Vol. 54; no. 1; pp. e2350616 - n/a
Main Authors: Hoorn, Iris A.E., Martynova, Evgenia, Subtil, Beatriz, Meek, Jelena, Verrijp, Kiek, Textor, Johannes, Flórez‐Grau, Georgina, Piet, Berber, den Heuvel, Michel M., Vries, I. Jolanda M., Gorris, Mark A. J.
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01-01-2024
Subjects:
CD14 antigen
CD19 antigen
CD1c antigen
Cell suspensions
Chemokine receptors
DCs
Dendritic cells
Immunity
Immunohistochemistry
Multiplex Immunohistochemistry
Phenotyping
Tumor markers
Tumor Microenvironment
Tumors
Tumor Microenvironment
DCs
Multiplex Immunohistochemistry
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Summary: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. In this paper, we describe the development, validation, and quantitative analysis of a multiplex immunohistochemistry panel pipeline with which conventional type 1 dendritic cells (cDC1s), cDC2s, and plasmacytoid DCs can be detected in the spatial context of the tumor microenvironment.
Bibliography:I. Jolanda M. de Vries and Mark A. J. Gorris shared the last authorship.
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ISSN:0014-2980
1521-4141
DOI:10.1002/eji.202350616