Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.

Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immu...

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Autores principales: Lei Huang, Ramireddy Bommireddy, Luis E Munoz, Rohini N Guin, Changyong Wei, Amanda Ruggieri, Ashwathi P Menon, Xiaoxian Li, Mala Shanmugam, Taofeek K Owonikoko, Suresh S Ramalingam, Periasamy Selvaraj
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/dc6e930ff2a44d15a2ac8e0dd7a119d8
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spelling oai:doaj.org-article:dc6e930ff2a44d15a2ac8e0dd7a119d82021-12-02T20:14:58ZExpression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.1932-620310.1371/journal.pone.0254125https://doaj.org/article/dc6e930ff2a44d15a2ac8e0dd7a119d82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254125https://doaj.org/toc/1932-6203Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immune responses in immunocompetent syngeneic tumor transplant models and augment the efficacy of experimental drugs. In this study, we show that the growth rate of Lewis lung carcinoma (LL/2) tumors was reduced after transduction of tdTomato and luciferase (tdTomato/Luc) compared to the parental cell line. tdTomato/Luc expression by LL/2 cells altered the tumor microenvironment by increasing tumor-infiltrating lymphocytes (TILs) while inhibiting tumor-induced myeloid-derived suppressor cells (MDSCs). Interestingly, tdTomato/Luc expression did not alter the response of LL/2 tumors to anti-PD-1 and anti-CTLA-4 antibodies. These results suggest that the use of tdTomato/Luc-transduced cancer cells to conduct studies in immune competent mice may lead to cell-extrinsic tdTomato/Luc-induced alterations in tumor growth and tumor immune microenvironment that need to be taken into consideration when evaluating the efficacy of anti-cancer drugs and vaccines in immunocompetent animal models.Lei HuangRamireddy BommireddyLuis E MunozRohini N GuinChangyong WeiAmanda RuggieriAshwathi P MenonXiaoxian LiMala ShanmugamTaofeek K OwonikokoSuresh S RamalingamPeriasamy SelvarajPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254125 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lei Huang
Ramireddy Bommireddy
Luis E Munoz
Rohini N Guin
Changyong Wei
Amanda Ruggieri
Ashwathi P Menon
Xiaoxian Li
Mala Shanmugam
Taofeek K Owonikoko
Suresh S Ramalingam
Periasamy Selvaraj
Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
description Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immune responses in immunocompetent syngeneic tumor transplant models and augment the efficacy of experimental drugs. In this study, we show that the growth rate of Lewis lung carcinoma (LL/2) tumors was reduced after transduction of tdTomato and luciferase (tdTomato/Luc) compared to the parental cell line. tdTomato/Luc expression by LL/2 cells altered the tumor microenvironment by increasing tumor-infiltrating lymphocytes (TILs) while inhibiting tumor-induced myeloid-derived suppressor cells (MDSCs). Interestingly, tdTomato/Luc expression did not alter the response of LL/2 tumors to anti-PD-1 and anti-CTLA-4 antibodies. These results suggest that the use of tdTomato/Luc-transduced cancer cells to conduct studies in immune competent mice may lead to cell-extrinsic tdTomato/Luc-induced alterations in tumor growth and tumor immune microenvironment that need to be taken into consideration when evaluating the efficacy of anti-cancer drugs and vaccines in immunocompetent animal models.
format article
author Lei Huang
Ramireddy Bommireddy
Luis E Munoz
Rohini N Guin
Changyong Wei
Amanda Ruggieri
Ashwathi P Menon
Xiaoxian Li
Mala Shanmugam
Taofeek K Owonikoko
Suresh S Ramalingam
Periasamy Selvaraj
author_facet Lei Huang
Ramireddy Bommireddy
Luis E Munoz
Rohini N Guin
Changyong Wei
Amanda Ruggieri
Ashwathi P Menon
Xiaoxian Li
Mala Shanmugam
Taofeek K Owonikoko
Suresh S Ramalingam
Periasamy Selvaraj
author_sort Lei Huang
title Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
title_short Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
title_full Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
title_fullStr Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
title_full_unstemmed Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
title_sort expression of tdtomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/dc6e930ff2a44d15a2ac8e0dd7a119d8
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