Using the Spleen as an In Vivo Systemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy with α-PD-L1
Joint Authors
Kleinerman, Eugenie S.
Lindsey, Brock A.
Markel, Justin E.
Noore, Jabeen
Emery, Eric J.
Bobnar, Harley J.
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-12-12
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Indications for immunotherapies are still unclear, and there is a great need for real-time patient immune status monitoring.
In this study, we confirmed that the local and systemic immune profiles of an orthotopic osteosarcoma model with or without luciferase transfection were statistically equivalent.
Next, we used flow cytometry to describe systemic immune cell populations influenced by osteosarcoma disease progression.
When compared to vehicle-inoculated sham mice, it was found that tumor-bearing mice had significant immunophenotype disturbances at approximately 11 weeks after inoculation (at which time 90% of primary tumor-bearing mice have fulminant pulmonary metastases).
Percent populations of natural killer cells and T regulatory cells were increased in the spleens of tumor-bearing mice (p<0.0083) compared to shams.
Additionally, T lymphocytes from spleens of tumor-bearing mice showed increased Tim-3/PD-1 exhaustion status (p<0.0083).
There were also increases in the percent populations of myeloid cells and overall M1/M2 macrophage marker expression on tumor-bearing mice spleens versus controls (p<0.00714).
Finally, treatment with 20 μg α-PD-L1 decreased T-cell exhaustion back to sham status, with a corresponding increase in CTLA-4 expression on cytotoxic T cells in the majority of mice tested.
Checkpoint inhibition also increased splenic monocyte maturation and returned macrophage M1/M2 marker expression back to sham status.
These data suggest that cancer induces systemic immune dysregulation and that these changes may be elucidated and utilized for treatment purposes by sampling the systemic immune environment via the spleen.
In addition, treatment with the checkpoint inhibitor α-PD-L1 may neutralize but not overcome the systemic immunological changes induced by a progressing malignancy.
American Psychological Association (APA)
Markel, Justin E.& Noore, Jabeen& Emery, Eric J.& Bobnar, Harley J.& Kleinerman, Eugenie S.& Lindsey, Brock A.. 2018. Using the Spleen as an In Vivo Systemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy with α-PD-L1. Complexity،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1212840
Modern Language Association (MLA)
Markel, Justin E.…[et al.]. Using the Spleen as an In Vivo Systemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy with α-PD-L1. Complexity No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1212840
American Medical Association (AMA)
Markel, Justin E.& Noore, Jabeen& Emery, Eric J.& Bobnar, Harley J.& Kleinerman, Eugenie S.& Lindsey, Brock A.. Using the Spleen as an In Vivo Systemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy with α-PD-L1. Complexity. 2018. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1212840
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212840