Combined locoregional-immunotherapy for liver cancer

Abstract

Locoregional therapies are commonly used to treat patients with hepatocellular carcinoma. It has been noted for many years that locoregional therapies may have additional systemic effects other than simple tumour elimination. Immunological "side effects" have been described in response to locoregional therapies in animal studies and in patients. With the advent of immunotherapy for hepatocellular carcinoma, there is increasing interest in determining the best way to combine immunotherapy with locoregional therapies. Herein, we provide a compact summary of answered and unanswered questions in the field, including: What animal model is best suited to test combined immune-locoregional treatments? How does tumour cell death affect immune responses? What type of immune responses have been observed in patients treated with different types of locoregional therapies? What can be surmised from the results of the first study testing the combination of locoregional therapy with immune checkpoint blockade? Finally, we discuss the outlook for this rapidly growing area of research, focussing on the issues which must be overcome to bridge the gap between interventional radiology and cancer immunology.

Keywords: Cell death; Locoregional therapy; Radiofrequency ablation; T cell; Tumour immunology.

Figure 1:

Spontaneous HCC developing in chronically hepatitis infected woodchucks. (A) Contrast-enhanced CT scan shows large heterogenous tumor with robust arterial blood supply (B). Gross pathology of liver and tumor (tumor edges demarcated by white arrows, margins of the tumor behind the liver demarcated by dashed line).

Figure 2:

Overview of considerations for future research studies combining immunotherapy with locoregional therapies

Figure 3:

Tumor response in HCC patient upon TACE + tremelimumab treatment in lesion not treated by TACE.