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Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice

SIMPLE SUMMARY: Immunotherapies have revolutionized the field of oncology and have been approved to treat cancer. Despite progress in immunotherapy, many challenges remain, including the identification (i) of predictive markers for treatment response or (ii) of beneficial T cell subsets involved in...

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Autores principales: Bruss, Christina, Kellner, Kerstin, Ortmann, Olaf, Seitz, Stephan, Brockhoff, Gero, Hutchinson, James A., Wege, Anja Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103756/
https://www.ncbi.nlm.nih.gov/pubmed/35565343
http://dx.doi.org/10.3390/cancers14092214
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author Bruss, Christina
Kellner, Kerstin
Ortmann, Olaf
Seitz, Stephan
Brockhoff, Gero
Hutchinson, James A.
Wege, Anja Kathrin
author_facet Bruss, Christina
Kellner, Kerstin
Ortmann, Olaf
Seitz, Stephan
Brockhoff, Gero
Hutchinson, James A.
Wege, Anja Kathrin
author_sort Bruss, Christina
collection PubMed
description SIMPLE SUMMARY: Immunotherapies have revolutionized the field of oncology and have been approved to treat cancer. Despite progress in immunotherapy, many challenges remain, including the identification (i) of predictive markers for treatment response or (ii) of beneficial T cell subsets involved in tumor elimination. “Humanized” mice are a promising translational model for studying the human immune system in the context of immuno-oncology research. Here, multicolor flow cytometry was applied to characterize immune cell subsets in the spleen of humanized mice transplanted with patient-derived breast cancer tissues. This multicolor immune cell setup will help to identify promising therapeutic approaches or predictive immune cell subsets in the future using humanized tumor mice. ABSTRACT: “Humanized” mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34(+) stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34(+) cells. Contamination ≤ 1.2% by CD3(+) cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes.
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spelling pubmed-91037562022-05-14 Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice Bruss, Christina Kellner, Kerstin Ortmann, Olaf Seitz, Stephan Brockhoff, Gero Hutchinson, James A. Wege, Anja Kathrin Cancers (Basel) Article SIMPLE SUMMARY: Immunotherapies have revolutionized the field of oncology and have been approved to treat cancer. Despite progress in immunotherapy, many challenges remain, including the identification (i) of predictive markers for treatment response or (ii) of beneficial T cell subsets involved in tumor elimination. “Humanized” mice are a promising translational model for studying the human immune system in the context of immuno-oncology research. Here, multicolor flow cytometry was applied to characterize immune cell subsets in the spleen of humanized mice transplanted with patient-derived breast cancer tissues. This multicolor immune cell setup will help to identify promising therapeutic approaches or predictive immune cell subsets in the future using humanized tumor mice. ABSTRACT: “Humanized” mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34(+) stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34(+) cells. Contamination ≤ 1.2% by CD3(+) cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes. MDPI 2022-04-28 /pmc/articles/PMC9103756/ /pubmed/35565343 http://dx.doi.org/10.3390/cancers14092214 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bruss, Christina
Kellner, Kerstin
Ortmann, Olaf
Seitz, Stephan
Brockhoff, Gero
Hutchinson, James A.
Wege, Anja Kathrin
Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title_full Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title_fullStr Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title_full_unstemmed Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title_short Advanced Immune Cell Profiling by Multiparameter Flow Cytometry in Humanized Patient-Derived Tumor Mice
title_sort advanced immune cell profiling by multiparameter flow cytometry in humanized patient-derived tumor mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103756/
https://www.ncbi.nlm.nih.gov/pubmed/35565343
http://dx.doi.org/10.3390/cancers14092214
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