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Sci Rep ; 9(1): 14640, 2019 10 10.
Article in English | MEDLINE | ID: mdl-31601975

ABSTRACT

Non-small cell lung cancer (NSCLC) causes 19% of all Australian cancer deaths, with a 5-year survival post-resection of around 60%. Post-operative recurrence is due to metastases that were undetectable pre-operatively, or growth of microscopic locoregional residual disease. However, post-operative imaging modalities typically only detect more advanced tumours; where PET-CT has a detection limit of 6-7 mm. Detection of small deposits of lung metastatic disease is of importance in order to facilitate early and potentially more effective treatment. In this study, in a murine model of lung metastatic disease, we explore whether neo-antigen specific T cells are a sensitive marker for the detection of lung cancer after primary tumour resection. We determine lung metastatic disease by histology, and then compare detection by PET-CT and neo-antigen specific T cell frequency. Detection of lung metastatic disease within the histology positive group by PET-CT and neo-antigen specific T cell frequency were 22.9% and 92.2%, respectively. Notably, neo-antigen specific T cells in the lung draining lymph node were indicative of metastatic disease (82.8 ± 12.9 spots/105 cells; mean ± SE), compared to healthy lung control (28.5 ± 8.6 spots/105 cells; mean ± SE). Potentially, monitoring tumour neo-antigen specific T cell profiles is a highly sensitive method for determining disease recurrence.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/pathology , Lymphatic Metastasis/diagnosis , Lymphocytes, Tumor-Infiltrating/immunology , T-Lymphocytes/immunology , Aged , Animals , Antigens, Neoplasm/immunology , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Non-Small-Cell Lung/surgery , Cell Line, Tumor/transplantation , Disease Models, Animal , Enzyme-Linked Immunospot Assay , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Lymph Nodes/cytology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Mice , Middle Aged , Pneumonectomy , Positron Emission Tomography Computed Tomography , Treatment Outcome
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