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.
Highlights
More than 15 million cancer patients undergo resection of their tumour every year[1]
We show that increased T cell responses to neo-antigen are a sensitive marker of early metastatic lung disease, and that responses to a combination of several tumour specific neo-antigen T cell responses performed even better than single neo-antigen responses as an sensitive method of detection of metastatic lung disease compared to PET-CT
We noted that approximately half of the mice had developed metastatic lung disease by day 19 post-surgery, with tumours in the range 2.9–30.0 × 107 photons/sec as determined by In Vivo Imaging Systems (IVIS) (Fig. 1B)
Summary
More than 15 million cancer patients undergo resection of their tumour every year[1]. Immunotherapy is a breakthrough modality for the treatment of a number of cancers, and works best when tumour deposits are relatively small[5]. 5-year survival after resection is approximately 60%9, indicating that current curative-intent treatment has limited efficacy and that residual microscopic tumour deposits remain undetected. Imaging modalities are typically used to detect the presence of metastatic disease, it is known to miss small deposits. Given the proportion of patients who go on to develop metastatic disease post-resection, current imaging modalities miss a large proportion of the microdeposits of tumour that are present[2,10]. Any such T cells detected could be a memory population, driven by the original tumour that was resected and not reflective of the presence of metastases at all
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