Current landscape of cross-line immune checkpoint blockade for cancer treatment

Substantial advances from bench to bedside have arisen in the realm of cancer immunotherapy, endowing unprecedented survival benefits and even curing a minor subset of patients with advanced cancer. However, the clinical application of immune checkpoint blockade (ICB) is impeded by several critical challenges, and it tends to be dismissed after disease progression or severe immune-related adverse events following previous ICB attempt. Pursuing further augmentation of ICB efficacy and optimization of overall prognosis, cross-line immunotherapy has emerged as a promising rechallenging tactic for patients who are refractory, relapsed or intolerant to prior ICB. By far, cross-line immunotherapy remains immature and controversial due to the absence of a constructed framework, comprehensive profiling and convincing evidence. In this review, we delve into this burgeoning field from conventional ICB to cross-line immunotherapy, elucidating the current landscape, latest explorations, practical hurdles, viable counteractions and future perspectives. Characterizing the rationales would update our knowledge and unveil the latent therapeutic potential of cross-line immunotherapy, thereby benefiting post-ICB patients to the utmost.