Remarkable response to durvalumab and tremelimumab in a patient with hepatocellular carcinoma: a case report

Predictive biomarkers for the efficacy of tremelimumab, a cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor, in hepatocellular carcinoma (HCC) have not yet been identified.

We report a case of HCC in which switching from bevacizumab plus atezolizumab to tremelimumab plus durvalumab after disease progression resulted in marked tumor regression, accompanied by the development of immune-related adverse event hepatitis. To explore the underlying mechanism, we performed immunohistochemical analysis of CD80, CD86, CD31, and CD3 expression in HCC tissue samples from 15 patients, including the present case.

Immunohistochemistry for PD-L1 showed no detectable expression in the tumor tissue. CD80 (a co-stimulatory molecule that binds to CD28 and CTLA-4) was strongly expressed in hepatoma cells, with higher levels compared to the other cases. In contrast, CD86 (another co-stimulatory molecule) was observed in non-parenchymal cells, with relatively low expressions in this case. Similarly, the expression levels of CD31 (microvessel density marker) and CD3 (T lymphocyte marker) were also low.

Strong expressions of CD80 may have contributed to the therapeutic response by shifting its binding from CTLA-4 to CD28 following CTLA-4 blockade, thereby promoting T cell activation. CD80 expression may serve as a predictive biomarker for the efficacy of CTLA-4 blockade therapy.