Simultaneous blockade of TIGIT and HIF-1α induces synergistic anti-tumor effect and decreases the growth and development of cancer cells

Purpose: T-cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint that is overexpressed on both immune cells and some cancer cells. TIGIT can alter the anti-tumor responses inside the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1 alpha) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1 alpha can enhance the expression of different immune checkpoints. Accordingly, hypoxic TME and TIGIT overexpression cause cancer development. Thus, we decided to inhibit tumor cell expansion by inhibiting TIGIT and HIF-1 alpha molecules and discovering the relationship between TIGIT and HIF-1 alpha. Methods: In this research, we utilized superparamagnetic iron oxide-based NPs (SPIONs) combined with chitosan lactate (CL) and folic acid (FA) nanoparticles (NPs) loaded with TIGIT-siRNA and HIF-1 alpha-siRNA for suppressing TIGIT and HIF-1 alpha in tumor cells and evaluated the consequences of this treatment strategy on tumor growth, apoptosis, and metastasis. Results: The results showed that cancer cells treated with TIGIT and HIF-1 alpha siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1 alpha expression, colony formation ability, angiogenesis, and the growth rate of cancer cells. Conclusions: Present data suggest the combination treatment of TIGIT and HIF-1 alpha as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1 alpha inside the TME.

Automated summary

Inhibiting TIGIT and HIF-1 alpha can effectively suppress tumor growth, reduce angiogenesis, and significantly impact the growth rate of cancer cells, demonstrating the potential of combination therapy targeting TIGIT and HIF-1 alpha.