954P - Evaluation of antigen-specific CD8 T cell responses to predict efficacy of atezolizumab and bevacizumab treatment in hepatocellular carcinoma

Background

The development of immunotherapy allows improvement of survival in advanced hepatocellular carcinoma (HCC). However, objective responses occur only in a third of patients and the identification of biomarkers to predict therapeutic efficacy remains a major issue. In this setting, we developed an immunological monitoring evaluating the CD8 specific immune responses of selected tumor-shared antigens.

Methods

Twenty patients with advanced HCC treated with atezolizumab and bevacizumab in a first-line setting were included in the ITHER study (NCT02840058). Peripheral blood mononuclear cells were analyzed before and after 3 months of atezolizumab and bevacizumab. CD8 specific immune responses of various antigens (telomerase, survivin, NY-ESO-1, mage-A1, mage-A3, and glypican) were evaluated by IFNγ ELISpot assays and correlated with clinical outcomes. Ten healthy donors (HD) were included in a control cohort.

Results

HCC patients had mostly a locally advanced tumor (70.0%) associated with cirrhosis (63.3%) and preserved liver function (88.9% Child-Pugh A). The frequencies of mage-A1, mage-A3, and glypican specific CD8 T-cell responses were higher in HCC patients than in HD (26.3% vs 10.0% for mage-A1, 15.8% vs 10.0% for mage-A3, and 27.8% vs 10.0% for glypican). At baseline, responder HCC patients had a higher frequency of mage-A1 specific CD8 T-cell responses than non-responders (40.0% vs 12.5%, p=0.313). Interestingly, the survivin (63.6% vs 0.0%, p=0.005) and NY-ESO-1 (40.0% vs 0.0%, p=0.092) specific CD8 T-cell responses were only observed in responder HCC patients. After immunotherapy, the frequency of these specific responses was higher in responders compared to non-responder HCC patients in particular for survivn (50.0% vs 11.1%, p=0.141) and only observed in responder HCC patients for mage (33.3% vs 0.0%, p=0.206) and glypican (33.3% vs 0.0%, p=0.206).

Conclusions

The expansion of selected antigen specific CD8 T cells in HCC patients treated by immunotherapy provides the rationale for the immunological monitoring in this setting and deserves further investigation in a larger number of patients.

Clinical trial identification

NCT02840058.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.