Likewise, the resistance to immunotherapy may be acquired as a result of immune cells depletion within the tumor, as well as overexpression of genes encoding alternative immune checkpoint receptors (TIM-3, LAG-3, BTLA, TIGIT and VISTA) that inhibit the immune response and are associated with adaptive resistance to anti-PD-1 therapy in NSCLC patients [29,46]. This evidence concerns the gene PDCD1 and non-small cell lung carcinoma.