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 OutcomeABSTRACT
A blinded, randomised clinical trial was carried out in Brittany, France on three commercial pig farms with a history of pneumonia. Pigs with clinical signs of respiratory disease were randomly allocated to one of two treatment groups; 100 pigs received a single intramuscular injection of a long-acting formulation of tylosin at a dose rate of 20 mg tylosin/kg bodyweight, and 101 pigs received three consecutive daily intramuscular injections of 10 mg tylosin/kg bodyweight. The pigs' rectal temperatures and other clinical variables were recorded at intervals and a scoring system was used to evaluate the results of the treatments. Relapses were recorded for up to nine days after the treatment. There were no statistically significant differences between the two treatments in terms of clinical scores, rectal temperatures, or cure or relapse rates.
