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

Autor: Xiaoxian Li, Ashwathi P. Menon, Mala Shanmugam, Suresh S. Ramalingam, Taofeek K. Owonikoko, Lei Huang, Ramireddy Bommireddy, Periasamy Selvaraj, Rohini N. Guin, Amanda Ruggieri, Changyong Wei, Luis E. Munoz
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Lung Neoplasms
Gene Expression
Biochemistry
Lung and Intrathoracic Tumors
Carcinoma
Lewis Lung
Mice
White Blood Cells
Spectrum Analysis Techniques
Genes
Reporter
Animal Cells
Tumor Microenvironment
Medicine and Health Sciences
Cytotoxic T cell
Luciferases
Multidisciplinary
biology
T Cells
Flow Cytometry
Enzymes
Oncology
Spectrophotometry
Medicine
Cytophotometry
Antibody
Cellular Types
Oxidoreductases
Luciferase
Research Article
Imaging Techniques
Immune Cells
Science
Immunology
Cytotoxic T cells
Research and Analysis Methods
Immune system
Cell Line
Tumor
Fluorescence Imaging
medicine
Animals
Molecular Biology Techniques
Molecular Biology
Tumor microenvironment
Blood Cells
Lewis lung carcinoma
Cancer
Cancers and Neoplasms
Biology and Life Sciences
Proteins
Cell Biology
medicine.disease
Luminescent Proteins
Tumor progression
Cancer cell
biology.protein
Cancer research
Enzymology
Cloning
Zdroj: PLoS ONE, Vol 16, Iss 8, p e0254125 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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