Engineering the Tumor Immune Microenvironment through Minimally Invasive Interventions

SIMPLE SUMMARY: Interventional radiology is a highly evolving field that can modulate the various barriers imposed by the immunosuppressive tumor microenvironment. This review aims to showcase the various immune biophysical barriers that limit anti-cancer therapy by the tumor microenvironment and how interventional radiology possesses the facilities to overcome these barriers. These tools involve both physical and immune therapies that can be intratumorally injected to act locally but recruit a systemic response to produce a more potentiated anti-cancer therapeutic response. ABSTRACT: The tumor microenvironment (TME) is a unique landscape that poses several physical, biochemical, and immune barriers to anti-cancer therapies. The rapidly evolving field of immuno-engineering provides new opportunities to dismantle the tumor immune microenvironment by efficient tumor destruction. Systemic delivery of such treatments can often have limited local effects, leading to unwanted offsite effects such as systemic toxicity and tumor resistance. Interventional radiologists use contemporary image-guided techniques to locally deliver these therapies to modulate the immunosuppressive TME, further accelerating tumor death and invoking a better anti-tumor response. These involve local therapies such as intratumoral drug delivery, nanorobots, nanoparticles, and implantable microdevices. Physical therapies such as photodynamic therapy, electroporation, hyperthermia, hypothermia, ultrasound therapy, histotripsy, and radiotherapy are also available for local tumor destruction. While the interventional radiologist can only locally manipulate the TME, there are systemic offsite recruitments of the immune response. This is known as the abscopal effect, which leads to more significant anti-tumoral downstream effects. Local delivery of modern immunoengineering methods such as locoregional CAR-T therapy combined with immune checkpoint inhibitors efficaciously modulates the immunosuppressive TME. This review highlights the various advances and technologies available now to change the TME and revolutionize oncology from a minimally invasive viewpoint.