Sadly, even if immune cells seem to be abundant in biopsy, tumours can be or become resistant to ICIs due to upregulation of alternative checkpoints (TIM3 (T cell immunoglobulin and mucin-domain containing-3), LAG3 (lymphocyte-activation gene 3), and TIGIT (T cell immunoreceptor with Ig and ITIM domains)) and/or by using non-PD-1/CTLA4-mediated inhibitory pathways [11,12]. The gene discussed is LAG3; the disease is neoplasm.