Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer
Abstract Background Because patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs are regarded as lacking an immune microenvironment. However, whether patients’ immune cells co-exist in PDXs remains uncharacterized. Methods We cultured small pieces of lung PDX tissue in...
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doaj-6894e6771c634171aa7604d1ac710e1d2020-11-25T01:12:32ZengBMCJournal of Translational Medicine1479-58762018-11-0116111210.1186/s12967-018-1704-3Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancerXingxiang Pu0Ran Zhang1Li Wang2Yungchang Chen3Yi Xu4Apar Pataer5Ismail M. Meraz6Xiaoshan Zhang7Shuhong Wu8Lin Wu9Dan Su10Weimin Mao11John V. Heymach12Jack A. Roth13Stephen G. Swisher14Bingliang Fang15Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityDepartment of Pathology, Zhejiang Cancer HospitalDepartment of Thoracic Surgery, Zhejiang Cancer HospitalDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer CenterAbstract Background Because patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs are regarded as lacking an immune microenvironment. However, whether patients’ immune cells co-exist in PDXs remains uncharacterized. Methods We cultured small pieces of lung PDX tissue in media containing human interleukin-2 and characterized the proliferated lymphocytes by flow cytometric assays with antibodies specific for human immune cell surface markers. Presence of immune cells in PDXs was also determined by immunohistochemical staining. Results Human tumor-infiltrating lymphocytes (TILs) were cultured from nine of 25 PDX samples (36%). The mean time of PDX growth in immunodeficient mice before obtaining TILs in culture was 113 days (range 63–292 days). The TILs detected in PDXs were predominantly human CD8+ T cells, CD4+ T cells, or CD19+ B cells, depending on cases. DNA fingerprint analysis showed that the TILs originated from the same patients as the PDXs. Further analysis of two PDX-derived CD8+ T cells showed that they were PD-1−, CD45RO+, and either CD62L+ or CD62L−, suggesting they were likely memory T cells. Immunohistochemical staining showed that human T cells (CD8+ or CD4+), B cells (CD19+), and macrophages (CD68+) were present in stroma or intraepithelial cancer structures and that human PD-L1 was expressed in stromal cells. Moreover, the patient-derived immune cells in PDX can be passaged to the F2 generation and may migrate to spleens of PDX-bearing mice. Conclusions Patient-derived immune cells co-exist in early passages of PDXs in some lung cancer PDX models. The CD8+ cells from PDXs were likely memory T cells. These results suggest that PDXs can be used for evaluating the functionality of immune components in tumor microenvironments.http://link.springer.com/article/10.1186/s12967-018-1704-3Lung cancerPatient-derived xenografts (PDX)Tumor modelsTumor-infiltrating lymphocytesImmunotherapyTumor microenvironment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xingxiang Pu Ran Zhang Li Wang Yungchang Chen Yi Xu Apar Pataer Ismail M. Meraz Xiaoshan Zhang Shuhong Wu Lin Wu Dan Su Weimin Mao John V. Heymach Jack A. Roth Stephen G. Swisher Bingliang Fang |
spellingShingle |
Xingxiang Pu Ran Zhang Li Wang Yungchang Chen Yi Xu Apar Pataer Ismail M. Meraz Xiaoshan Zhang Shuhong Wu Lin Wu Dan Su Weimin Mao John V. Heymach Jack A. Roth Stephen G. Swisher Bingliang Fang Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer Journal of Translational Medicine Lung cancer Patient-derived xenografts (PDX) Tumor models Tumor-infiltrating lymphocytes Immunotherapy Tumor microenvironment |
author_facet |
Xingxiang Pu Ran Zhang Li Wang Yungchang Chen Yi Xu Apar Pataer Ismail M. Meraz Xiaoshan Zhang Shuhong Wu Lin Wu Dan Su Weimin Mao John V. Heymach Jack A. Roth Stephen G. Swisher Bingliang Fang |
author_sort |
Xingxiang Pu |
title |
Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
title_short |
Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
title_full |
Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
title_fullStr |
Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
title_full_unstemmed |
Patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
title_sort |
patient-derived tumor immune microenvironments in patient-derived xenografts of lung cancer |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2018-11-01 |
description |
Abstract Background Because patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs are regarded as lacking an immune microenvironment. However, whether patients’ immune cells co-exist in PDXs remains uncharacterized. Methods We cultured small pieces of lung PDX tissue in media containing human interleukin-2 and characterized the proliferated lymphocytes by flow cytometric assays with antibodies specific for human immune cell surface markers. Presence of immune cells in PDXs was also determined by immunohistochemical staining. Results Human tumor-infiltrating lymphocytes (TILs) were cultured from nine of 25 PDX samples (36%). The mean time of PDX growth in immunodeficient mice before obtaining TILs in culture was 113 days (range 63–292 days). The TILs detected in PDXs were predominantly human CD8+ T cells, CD4+ T cells, or CD19+ B cells, depending on cases. DNA fingerprint analysis showed that the TILs originated from the same patients as the PDXs. Further analysis of two PDX-derived CD8+ T cells showed that they were PD-1−, CD45RO+, and either CD62L+ or CD62L−, suggesting they were likely memory T cells. Immunohistochemical staining showed that human T cells (CD8+ or CD4+), B cells (CD19+), and macrophages (CD68+) were present in stroma or intraepithelial cancer structures and that human PD-L1 was expressed in stromal cells. Moreover, the patient-derived immune cells in PDX can be passaged to the F2 generation and may migrate to spleens of PDX-bearing mice. Conclusions Patient-derived immune cells co-exist in early passages of PDXs in some lung cancer PDX models. The CD8+ cells from PDXs were likely memory T cells. These results suggest that PDXs can be used for evaluating the functionality of immune components in tumor microenvironments. |
topic |
Lung cancer Patient-derived xenografts (PDX) Tumor models Tumor-infiltrating lymphocytes Immunotherapy Tumor microenvironment |
url |
http://link.springer.com/article/10.1186/s12967-018-1704-3 |
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