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recruited and divided into the experimental (combination of Pexa-Vec with BSC) and the control (BSC
alone) groups. Although Pexa-Vec was generally well-tolerated and could induce immune responses to
vaccinia and HCC associated antigens, it failed to enhance OS as a second-line treatment after sorafenib
failure. This class of oncolytic immunotherapy may benefit cancer patients with earlier disease stages and
[54]
the combination of this approach with other therapeutics needs to be investigated .

NCT03071094 is another trial to evaluate the safety and efficacy of Pexa-Vec plus PD-1 inhibitors as first-
line therapy for advanced HCC. However, no results have been released.

CONCLUSION
We have summarized the immunotherapy approaches for the treatment of HCC patients [Figure 1].
Increasing data provide evidence that HCC patients can benefit from different immunotherapies. Currently,
only anti-PD-1/PD-L1 antibodies have been approved to treat advanced HCC as a first-line therapy, while
other immunotherapy approaches are still in clinical trials. However, given that only a proportion of HCC
patients respond to anti-PD-1/PD-L1 antibodies, combination therapy will likely be the future. Final
results of ongoing trials are crucial for the design and development of further combination therapy in HCC
according to its efficacy and safety profile. In addition, future studies should explore biomarkers to predict
one’s response to immunotherapy in HCC, other than PD-L1 expression in terms of ICB therapy, novel
target antigens (neo-antigens) to prepare DC-based vaccines and CAR-T cells. Future clinical trials are
necessary. Indeed, we have opened the doors to immunotherapy and complete control of HCC may not a
dream.

DECLARATIONS
Authors’ contributions
Wrote the review: Ni L, Dong C
Helped with review writing: Feng Y

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by grants from Beijing Municipal Science and Technology (Grant No.
Z181100001318007) and National Natural Science Foundation of China (NSFC) (Grant No. 31991173).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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