Intratumoral Immunotherapy: A Potential Treatment for Gastrointestinal Malignancies

Take-Away Points

• ■ Major Focus: Intratumoral delivery of immunotherapeutic agents in gastrointestinal malignancies may help to overcome the low efficacy of systemically administered immunotherapies.

• ■ Key Result: This review highlights emerging preclinical and clinical evidence of using a variety of intratumoral injection techniques directly into the tumor microenvironment by using endoscopic image guidance or arterial delivery to enhance local and distant immunotherapeutic responses.

• ■ Impact: Intratumoral delivery alone or in combination with radiotherapy or chemotherapy may pave the way forward for producing robust immune responses for gastrointestinal malignancies.

Immune checkpoint blockade has become a powerful therapeutic approach for several malignancies. For gastrointestinal malignancies, many agents have gained U.S. Food and Drug Administration approval and have been shown to be particularly effective for high micro-satellite instability (MSI)—status tumors. However, few gastrointestinal cancers exhibit high MSI status, and the overall effect size of immune checkpoint blockade remains relatively small in several phase III clinical trials for gastrointestinal cancers.

Yang et al reviewed the emerging field of intratumoral delivery of immunotherapeutics, highlighting the use of endoscopic imaging or arterial injection applications for interventionalists to deliver immunotherapeutic agents directly into the tumor microenvironment. This local approach confers several potential distinct advantages, which include reducing systemic toxicities, inducing a T-cell response without needing to first extract specific tumor antigens, and harnessing a possible abscopal effect—the potential to treat distant areas of cancer through an activated immune response.

Yang and colleagues discuss several potential injectable immunotherapeutic and immunostimulatory agents for intratumoral injections. For example, viral vectors encoding proinflammatory cytokines, such as IL-12 and interferon-γ, have been shown to completely ablate tumors in animal models. Lyophilized bacteria, such as Streptococcus pyogenes, can also be injected into the tumor microenvironment to induce proinflammatory reactions. Direct intratumoral injection of dendritic cells can improve antigen presentation and have shown initial promise in animal models and a few clinical case series. And lastly, phase II clinical trials are underway exploring approaches for endoscopically guided injection of autologous tumor cell—stimulated T cells.

This review highlights the early results of a promising variation to immunotherapy in which multiple different types of cells and immunostimulatory agents can be injected directly into the tumor. The authors also highlight that this approach can be combined with either chemo-therapy and/or radiotherapy, where the abscopal effect could potentially be enhanced with combination therapy approaches. It will be exciting to see how these initial results can shape the future of immunotherapy moving forward and how interventional radiologists and gastroenterologists can play a crucial role in the delivery of these therapies.

Highlighted Article

• Yang Q, Sheth RA, Tam A. Image-guided intratumoral delivery of immunotherapeutics in gastrointestinal malignancies. Dig Dis Interv 2021;05(01):022–031. doi: https://doi.org/10.1055/s-0040-1718389.