Programmed cell death protein 1 (PD-1) and Lymphocyte-activation gene 3 protein (LAG-3) (PD-1 and LAG-3)

Programmed cell death protein 1 (PD-1) and Lymphocyte-activation gene 3 protein (LAG-3) are co-inhibitory receptors primarily expressed on activated T cells, natural killer (NK) cells, and B cells [2, 13]. They function as immune checkpoints to maintain self-tolerance and prevent excessive immune responses, but their persistent expression in the tumor microenvironment leads to T-cell exhaustion and immune evasion by cancer cells [5, 12]. While PD-1 primarily restricts T-cell proliferation and survival, LAG-3 modulates T-cell effector functions such as cytotoxicity and cytokine production [5, 12]. Dual blockade of these pathways has demonstrated synergistic anti-tumor activity by reactivating exhausted T cells more effectively than monotherapy [10, 16]. This therapeutic strategy is clinically validated, notably with the FDA approval of the nivolumab and relatlimab combination (Opdualag) for advanced melanoma, and is being explored across various other malignancies [1, 7].

Other names

PDCD1CD279CD223LAG3Lymphocyte-activation gene 3

Dual blockade of PD-1 and LAG-3 inhibitory pathways to restore T-cell effector functions and reverse T-cell exhaustion.