As a type I transmembrane glycoprotein, the structural composition of PD-L1 directly determines the realization of its core functions. The IgV and IgC-like domains in the extracellular region are the key sites for its binding to the PD-1 receptor. The conformational stability of these two domains directly affects the binding affinity, thereby determining the transmission efficiency of the immunosuppressive signal. Although the intracellular domain is very short and lacks a well-recognized classical signaling function, a few studies suggest that it may participate in reverse signaling regulation. This potential function may indirectly affect the activation status or signal transduction of the cell itself. In addition, as a glycoprotein, its glycosylation modifications may affect its expression stability on the cell surface and its binding specificity, thereby influencing its role in tumor immune escape. These structural features provide a structural reference for the design of targeted drugs.

Inflammatory signal induction is one of the major driving mechanisms. The tumor microenvironment contains abundant inflammatory cytokines, among which IFNγ is a core inducing factor. It can promote the transcription and expression of the PD-L1 gene by activating downstream signaling pathways, leading to rapid upregulation of PD-L1 levels on tumor cells and forming an immunosuppressive barrier.

The indirect effect of oncogenic mutations within the tumor is another mechanism. After certain oncogenic mutations occur in tumor cells, they can indirectly promote PD-L1 expression by regulating intracellular signaling networks. This upregulation is persistent, allowing tumor cells to maintain an immune escape state over the long term. The combined action of these two driving mechanisms leads to high levels of PD-L1 expression in many solid tumors, and such high expression is often associated with tumor progression and an increased risk of metastasis, serving as an important reference indicator for patient prognosis.

After PD-L1 binds to PD-1 on the surface of T cells, it inhibits T cell function through a series of signaling processes, with specific effects manifested in multiple aspects. First, it blocks key signaling pathways downstream of the T cell receptor, such as the PI3K/AKT and Ras-MEK-ERK pathways. These two pathways are central to T cell proliferation and activation, and their blockade directly impairs T cell proliferation, preventing the expansion of a sufficient effector T cell population. Second, it inhibits the secretion of cytokines by T cells, reducing the production of pro-immune factors such as IFNγ and IL-2, thereby weakening the T cell's ability to recognize and transmit killing signals against tumor cells. Furthermore, the cytotoxic function of T cells is directly suppressed, rendering them unable to effectively lyse tumor cells. However, this suppression is reversible: when the PD-L1/PD-1 interaction is blocked, T cells can gradually recover their killing ability, which is the core mechanism of action of PD-L1 antibody therapy.

The complexity of the tumor microenvironment: in some tumors, the microenvironment contains a large number of immunosuppressive cells and factors. Even if the PD-L1/PD-1 interaction is blocked, T cells still struggle to overcome the immunosuppressive barrier and cannot effectively exert their killing function, leading to poor treatment response.

Heterogeneity of PD-L1 expression: PD-L1 expression levels vary among tumor cells in different regions of the same tumor tissue. Some tumor cells express low or no PD-L1, so monotherapy cannot target all tumor cells, resulting in limited therapeutic efficacy.

T cell exhaustion: T cells that have been chronically exposed to the tumor microenvironment become functionally exhausted. Even after the PD-L1-mediated suppression is relieved, they may not rapidly recover their killing function, which further affects the treatment response rate. This is an important reason why monotherapy often fails to achieve ideal results.