Image-Guided Intratumoral Immunotherapy: An Educational Review

-Overview of intratumoral immunotherapy and its relevance to interventional oncology.

-Mechanism and purpose of controlled release of immunotherapy.

-Role of imaging in intratumoral delivery.

-Future direction of intratumoral immunotherapy research.



Background:

Immune checkpoint inhibitors (ICI) have proven to be a revolutionary treatment for many cancer patients. Tumors evade the immune system through activation of critical checkpoints, preventing tumor cell recognition. ICI therapy inhibits this inappropriate checkpoint activation, such as binding of PD-1/L1 and CTLA-4 pathways, allowing launch of an antitumoral immune response. Unfortunately, efficacy of ICI is inconsistent.  Intratumoral immunoadjuvants may reduce tumor immunotherapy resistance and increase response to ICI treatment. As of 2024, 87 ongoing clinical trials are investigating this potential. We aim to review mechanisms and outcome data of combined intratumoral immunoadjuvant therapy and ICI, as well as approaches to increase efficacy of therapy delivery.


Clinical Findings/Procedure Details:

Intratumoral injection of an immunomodulatory agent facilitates both a local and systemic inflammatory response, causing an immune-permissive state. Current therapies under investigation include TLR agonists, stimulator of interferon gene agonists, and cytokines in conjunction with ICI.  Using the clinicaltrials.gov database, we find multiple early phase trials that demonstrate encouraging immunologic activity such as increased tumor response, intratumoral T cell concentrations, and cytokine modulation.

There are multiple methods to optimize intratumoral injections, including multi-side hole needles, radio-opaque agents, and hydrogel excipients to increase tumor targeting and injection retention. While intratumoral therapy was once limited to superficial or easily visualized lesions, current innovation on radiopaque treatments focuses on improved observation under imaging guidance.  This allows for treatment of difficult to access lesions, unlocking a new population of treatable patients and tumors.


Conclusion and/or Teaching Points:

This session reviews intratumoral immunology, current techniques in immunomodulatory intratumoral injections, and results of pre-clinical and clinical trials currently underway, with drug delivery and retention within tumors and optimization for different tumor types and locations.  As interventional radiologists improve image-guided intratumoral immunotherapy, this field has the potential to be a new standard of care, especially in patients who do not respond to systemic ICI therapies.