Cargando…

Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma

To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive...

Descripción completa

Detalles Bibliográficos
Autores principales: Altorki, Nasser K., Borczuk, Alain C., Harrison, Sebron, Groner, Lauren K., Bhinder, Bhavneet, Mittal, Vivek, Elemento, Olivier, McGraw, Timothy E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033258/
https://www.ncbi.nlm.nih.gov/pubmed/35385730
http://dx.doi.org/10.1016/j.celrep.2022.110639
_version_ 1784692844952289280
author Altorki, Nasser K.
Borczuk, Alain C.
Harrison, Sebron
Groner, Lauren K.
Bhinder, Bhavneet
Mittal, Vivek
Elemento, Olivier
McGraw, Timothy E.
author_facet Altorki, Nasser K.
Borczuk, Alain C.
Harrison, Sebron
Groner, Lauren K.
Bhinder, Bhavneet
Mittal, Vivek
Elemento, Olivier
McGraw, Timothy E.
author_sort Altorki, Nasser K.
collection PubMed
description To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression, an effector immune response is present but is effectively thwarted by the immune-suppressive elements.
format Online
Article
Text
id pubmed-9033258
institution National Center for Biotechnology Information
language English
publishDate 2022
record_format MEDLINE/PubMed
spelling pubmed-90332582022-04-22 Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma Altorki, Nasser K. Borczuk, Alain C. Harrison, Sebron Groner, Lauren K. Bhinder, Bhavneet Mittal, Vivek Elemento, Olivier McGraw, Timothy E. Cell Rep Article To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression, an effector immune response is present but is effectively thwarted by the immune-suppressive elements. 2022-04-05 /pmc/articles/PMC9033258/ /pubmed/35385730 http://dx.doi.org/10.1016/j.celrep.2022.110639 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Altorki, Nasser K.
Borczuk, Alain C.
Harrison, Sebron
Groner, Lauren K.
Bhinder, Bhavneet
Mittal, Vivek
Elemento, Olivier
McGraw, Timothy E.
Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title_full Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title_fullStr Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title_full_unstemmed Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title_short Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
title_sort global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033258/
https://www.ncbi.nlm.nih.gov/pubmed/35385730
http://dx.doi.org/10.1016/j.celrep.2022.110639
work_keys_str_mv AT altorkinasserk globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT borczukalainc globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT harrisonsebron globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT gronerlaurenk globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT bhinderbhavneet globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT mittalvivek globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT elementoolivier globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma
AT mcgrawtimothye globalevolutionofthetumormicroenvironmentassociatedwithprogressionfrompreinvasiveinvasivetoinvasivehumanlungadenocarcinoma