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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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0254125</identifier><identifier>PMID: 34411144</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2021-08, Vol.16 (8), p.e0254125-e0254125</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Huang et al 2021 Huang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c743t-67fe4216689ff1ab4df2df91588cafd4f40fc8934da9cedb183271720e9ce5483</citedby><cites>FETCH-LOGICAL-c743t-67fe4216689ff1ab4df2df91588cafd4f40fc8934da9cedb183271720e9ce5483</cites><orcidid>0000-0003-3130-0551 ; 0000-0002-4827-7282</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376001/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376001/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34411144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Lei</creatorcontrib><creatorcontrib>Bommireddy, Ramireddy</creatorcontrib><creatorcontrib>Munoz, Luis E</creatorcontrib><creatorcontrib>Guin, Rohini N</creatorcontrib><creatorcontrib>Wei, Changyong</creatorcontrib><creatorcontrib>Ruggieri, Amanda</creatorcontrib><creatorcontrib>Menon, Ashwathi P</creatorcontrib><creatorcontrib>Li, Xiaoxian</creatorcontrib><creatorcontrib>Shanmugam, Mala</creatorcontrib><creatorcontrib>Owonikoko, Taofeek K</creatorcontrib><creatorcontrib>Ramalingam, Suresh S</creatorcontrib><creatorcontrib>Selvaraj, Periasamy</creatorcontrib><title>Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor</title><title>PloS one</title><addtitle>PLoS One</addtitle><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. 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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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language | eng |
recordid | cdi_plos_journals_2562820683 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
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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