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Developing synthetic tools to decipher the tumor–immune interactome

The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor–immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based...

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Autores principales: Weizman, Orr-El, Luyten, Sophia, Lu, Peiwen, Song, Eric, Qin, Kai, Mostaghimi, Darius, Ring, Aaron M., Iwasaki, Akiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622925/
https://www.ncbi.nlm.nih.gov/pubmed/37871202
http://dx.doi.org/10.1073/pnas.2306632120
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author Weizman, Orr-El
Luyten, Sophia
Lu, Peiwen
Song, Eric
Qin, Kai
Mostaghimi, Darius
Ring, Aaron M.
Iwasaki, Akiko
author_facet Weizman, Orr-El
Luyten, Sophia
Lu, Peiwen
Song, Eric
Qin, Kai
Mostaghimi, Darius
Ring, Aaron M.
Iwasaki, Akiko
author_sort Weizman, Orr-El
collection PubMed
description The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor–immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell–immune cell contact in vivo in order to decipher the tumor–immune interactome. We call this approach, Tumor–Immune Interactome Non-biased Discovery Retroviral Reporter or TIINDRR. Using TIINDRR, we identify the tumor–immune interactomes that define immunological refractory and sensitive tumors and how different immunotherapies alter these interactions. Thus, TIINDRR provides a flexible and versatile tool for studying in-vivo tumor–immune cell interactions, aiding in the identification of biologically relevant information needed for the rational design of immune-based therapies.
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spelling pubmed-106229252023-11-04 Developing synthetic tools to decipher the tumor–immune interactome Weizman, Orr-El Luyten, Sophia Lu, Peiwen Song, Eric Qin, Kai Mostaghimi, Darius Ring, Aaron M. Iwasaki, Akiko Proc Natl Acad Sci U S A Biological Sciences The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor–immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell–immune cell contact in vivo in order to decipher the tumor–immune interactome. We call this approach, Tumor–Immune Interactome Non-biased Discovery Retroviral Reporter or TIINDRR. Using TIINDRR, we identify the tumor–immune interactomes that define immunological refractory and sensitive tumors and how different immunotherapies alter these interactions. Thus, TIINDRR provides a flexible and versatile tool for studying in-vivo tumor–immune cell interactions, aiding in the identification of biologically relevant information needed for the rational design of immune-based therapies. National Academy of Sciences 2023-10-23 2023-10-31 /pmc/articles/PMC10622925/ /pubmed/37871202 http://dx.doi.org/10.1073/pnas.2306632120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Weizman, Orr-El
Luyten, Sophia
Lu, Peiwen
Song, Eric
Qin, Kai
Mostaghimi, Darius
Ring, Aaron M.
Iwasaki, Akiko
Developing synthetic tools to decipher the tumor–immune interactome
title Developing synthetic tools to decipher the tumor–immune interactome
title_full Developing synthetic tools to decipher the tumor–immune interactome
title_fullStr Developing synthetic tools to decipher the tumor–immune interactome
title_full_unstemmed Developing synthetic tools to decipher the tumor–immune interactome
title_short Developing synthetic tools to decipher the tumor–immune interactome
title_sort developing synthetic tools to decipher the tumor–immune interactome
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622925/
https://www.ncbi.nlm.nih.gov/pubmed/37871202
http://dx.doi.org/10.1073/pnas.2306632120
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