Lung cancer remains the leading cause of cancer‐related death worldwide. The disease is classified into two major subtypes, small‐cell lung cancer (SCLC) and the more prevalent non‐small‐cell lung cancer (NSCLC). First‐line conventional therapies, such as chemotherapy, radiotherapy and surgery, have offered limited benefit, and patient prognosis remains poor with post‐treatment recurrences representing a major cause of morbidity. Consequently, there is an urgent need for improved therapeutic options. Historically, NSCLC has been considered a non‐immunogenic disease. However, increased understanding of tumor‐immune interactions has challenged this paradigm in both lung and other malignancies, with cancer elimination by tumor‐specific T cells increasingly well described in a myriad of solid tumors. Recent evidence has demonstrated that absent or weak anticancer responses are likely a product of tumor‐derived immunosuppression. This knowledge, along with a greater appreciation for the role of T cells in lung cancer elimination, has driven development of novel immunotherapeutic approaches which are demonstrating remarkable clinical efficacy. This review examines the role of T cells in lung cancer, discussing the direction and clinical significance of current and future immunotherapeutic strategies.

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.