Spontaneous Immune-mediated Regression Of Hepatocellular Carcinoma With High Tumor Mutational Burden

Abstract

Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related death in the United States and the fourth worldwide. Treatment of advanced HCC has been revolutionized in the past few years by combinations of therapies that stimulate the immune system to recognize and attack the cancer. The empirical success of this paradigm implies an immune-responsive nature of the HCC tumor microenvironment that can be pharmacologically manipulated. There have been small published series of spontaneous regressions of HCC lesions, and an obvious putative mechanism of such spontaneous HCC tumor regression involves immune rejection. One such recent case report described a series of six patients who experienced varying degrees of HCC tumor regression, one of whom had potentially unique features of the immune microenvironment. Here, we report a patient who experienced a spontaneous regression of an HCC lesion bearing a high tumor mutational burden (TMB) with a briskassociated lymphocytic infiltrate noted on a preoperative biopsy. We therefore propose a direct mechanism—immune recognition and clearance of a TMB-high tumor, with an unclear stimulus for such antitumor activity—that may underlie rare cases of spontaneous HCC regression.