Even if T cells can be activated within these immunosuppressive TMEs, lung tumor cells can exploit the homeostatic balance between costimulatory and coinhibitory signals, collectively referred to as coregulation.6 Costimulatory molecules such as CD28 and OX40 promote proliferation and survival.14 Conversely, coinhibitory molecules (immune checkpoints), such as CTLA‐4 and PD‐1, can induce T‐cell senescence and inactivation (Figure 4).14 Lung cancer cells can co‐opt these checkpoint pathways, with dysregulation to both the CTLA‐4 and PD‐1 axis well documented in lung cancer.24 This evidence concerns the gene CD28 and lung carcinoma.