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

Abstract

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-1α) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1α 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-1α molecules and discovering the relationship between TIGIT and HIF-1α.

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-1α- siRNA for suppressing TIGIT and HIF-1α 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-1α siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1α expression, colony formation ability, angiogenesis, and the growth rate of cancer cells.

Conclusions: Present data suggest the combination treatment of TIGIT and HIF-1α as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1α inside the TME.

Keywords: Cancer Immunotherapy; HIF-1α; Superparamagnetic iron oxide nanoparticles; TIGIT.