Can tissue-specific PD-1/PD-L1 targeting combined with other immune checkpoint blockades enhance immune clearance?

Age-related disorders are exacerbated by senescent cells (SnCs) due to their secretion of proinflammatory molecules, yet current therapeutic strategies have limited success in preclinical settings and clinical trials. A novel approach is needed to enhance SnCs clearance by targeting immune checkpoints, particularly the PD-1/PDL1 axis, combined with tissue-specific delivery of therapeutic agents. This strategy is critical in reducing the chronic inflammation and improving tissue health in aging populations. However, challenges such as immune evasion by SnCs and potential autoimmune responses must be addressed. The aim of this manuscript is to propose a combined approach to improve the efficacy of senolytic therapy.