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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Veröffentlicht in:PloS one 2021-08, Vol.16 (8), p.e0254125-e0254125
Hauptverfasser: Huang, Lei, Bommireddy, Ramireddy, Munoz, Luis E, Guin, Rohini N, Wei, Changyong, Ruggieri, Amanda, Menon, Ashwathi P, Li, Xiaoxian, Shanmugam, Mala, Owonikoko, Taofeek K, Ramalingam, Suresh S, Selvaraj, Periasamy
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container_title PloS one
container_volume 16
creator Huang, Lei
Bommireddy, Ramireddy
Munoz, Luis E
Guin, Rohini N
Wei, Changyong
Ruggieri, Amanda
Menon, Ashwathi P
Li, Xiaoxian
Shanmugam, Mala
Owonikoko, Taofeek K
Ramalingam, Suresh S
Selvaraj, Periasamy
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.
doi_str_mv 10.1371/journal.pone.0254125
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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Lei</au><au>Bommireddy, Ramireddy</au><au>Munoz, Luis E</au><au>Guin, Rohini N</au><au>Wei, Changyong</au><au>Ruggieri, Amanda</au><au>Menon, Ashwathi P</au><au>Li, Xiaoxian</au><au>Shanmugam, Mala</au><au>Owonikoko, Taofeek K</au><au>Ramalingam, Suresh S</au><au>Selvaraj, Periasamy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-08-19</date><risdate>2021</risdate><volume>16</volume><issue>8</issue><spage>e0254125</spage><epage>e0254125</epage><pages>e0254125-e0254125</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34411144</pmid><doi>10.1371/journal.pone.0254125</doi><tpages>e0254125</tpages><orcidid>https://orcid.org/0000-0003-3130-0551</orcidid><orcidid>https://orcid.org/0000-0002-4827-7282</orcidid><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects Animal models
Animals
Antibodies
Anticancer properties
Antitumor agents
Biology and Life Sciences
Bioluminescence
Cancer cells
Cancer vaccines
Carcinoma, Lewis Lung - genetics
Carcinoma, Lewis Lung - immunology
Cell growth
Cell Line, Tumor
Cloning
CTLA-4 protein
Development and progression
Diagnostic imaging
Drugs
Flow cytometry
Fluorescence
Funding
Gene Expression
Genes, Reporter - immunology
Genetic aspects
Genetic engineering
Growth rate
Health aspects
Hematology
Imaging techniques
Immune response
Immune system
Immunosuppressive agents
Immunotherapy
Laboratories
Luciferase
Luciferases - genetics
Luciferases - immunology
Luminescent Proteins - genetics
Luminescent Proteins - immunology
Lung cancer
Lung carcinoma
Lung diseases
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lymphocytes
Medicine
Medicine and Health Sciences
Methods
Mice
Oncology
Pathology
PD-1 protein
Penicillin
Proteins
Red Fluorescent Protein
Research and Analysis Methods
Suppressor cells
Tumor microenvironment
Tumor Microenvironment - genetics
Tumor Microenvironment - immunology
Tumor-infiltrating lymphocytes
Tumors
Vaccines
title Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor
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