Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1785130644654784512 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10622925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT weizmanorrel developingsynthetictoolstodecipherthetumorimmuneinteractome AT luytensophia developingsynthetictoolstodecipherthetumorimmuneinteractome AT lupeiwen developingsynthetictoolstodecipherthetumorimmuneinteractome AT songeric developingsynthetictoolstodecipherthetumorimmuneinteractome AT qinkai developingsynthetictoolstodecipherthetumorimmuneinteractome AT mostaghimidarius developingsynthetictoolstodecipherthetumorimmuneinteractome AT ringaaronm developingsynthetictoolstodecipherthetumorimmuneinteractome AT iwasakiakiko developingsynthetictoolstodecipherthetumorimmuneinteractome |