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As an immunosuppressive pathway, immune checkpoints are essential for maintaining autoimmune tolerance and regulating the duration and scope of immune responses in peripheral tissues.
On the other hand, due to the heterogeneity of tumors and the complexity of the tumor microenvironment (TME), the overall effective rate of immune checkpoint inhibitor therapy is low, and there is still room for improvement in many areas.
The entry of T cells into specific tissue sites involves complex signaling pathways between numerous cell types and soluble factors.
In terms of tumor vasculature, combination therapies targeting vascular endothelial cell growth factor (VEGF) or VEGF receptor (VEGFR) and PD-1, PDL-1 or PDL-2 are under evaluation, some of which are approved for clinical use treatment.
In addition to VEGF, the pro-angiogenic factor B-type endothelin receptor (ETBR) is another potential target for immune checkpoint inhibitor combination therapy.
Chemokines and cytokines are another focus of attention of researchers.
Even if T cells pass through many "obstacles" and finally enter TME, there are still many cytokines in TME, which can induce T cell failure and dysfunction.
The mononuclear phagocytic system (MPS) includes monocytes, macrophages and dendritic cells.
Take ALX Oncology’s research product ALX148 as an example.
We hope that more immune checkpoint inhibitors will come out soon and benefit more patients around the world.
Reference materials:
[1] Kubli, SP, Berger, T.