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Zhang et al. Hepatoma Res 2020;6:40 I http://dx.doi.org/10.20517/2394-5079.2020.20 Page 7 of 12

CONCLUSION AND OUTLOOK
Immunotherapies appear to be a promising treatment for advanced HCC. Multiple prospective studies are
attempting to validate the therapy outcomes with PD-1/PD-L1 and/or CTLA-4 blockade. However, only
a small proportion of HCC patients effectively respond to immunotherapies and much research is still
needed. One of the future directions for immunotherapies is combination therapies with other ICIs, TKIs,
vaccines, and oncolytic viruses, as well as conventional treatments in various stages of patients to improve
the antitumor efficacy. In addition, it is the important to research how to elevate immunotherapy efficacy
and ascertain the biomarkers of predictive therapeutic response to immunotherapy. For example, TMB has
been used in several tumor types to predict therapeutic response to anti-PD-1 therapy. In the future, we
expect to identify more predictive biomarker subsets which can be used to accurately evaluate the efficacy of
immunotherapy.

CAR-T technology and its application has been hailed as a scientific breakthrough in the field of hematological
tumors. Application of CAR-T therapy and TCR to treat HCC is expected to be a promising therapeutic
method. The crucial challenge is the need to identify specific antigens; overcome the TME, gut microbiome,
and HCC genomic features; and guard against adverse effects. Furthermore, the activation, proliferation,
and persistence of CAR-T immunotherapy should be considered with the outcomes of treatments for HCC.
In addition, standardization in the production of CAR-T and achieving individualized treatment should be
considered.

Different modifications of DC vaccine or DC-CIK therapy, such as selection of specific antigen targets and
appropriate immunologic adjuvant, may elevate the effectiveness and safety in further studies. Dendritic cells
lead to an increase in the naturally occurring neoantigen-specific immune response as well as the diversity of
neoantigens. The combination of DC vaccination with other immunotherapies, e.g., TCR-T, may be a novel
treatment modality in the future.

Because of the heterogeneity of tumor cells and the complexity of immuno-regulatory mechanisms,
multimodality therapies based on immunotherapy represent the next step in clinical antitumor efficacy,
which will enable advancing the field and improving the outcomes of HCC patients.

DECLARATIONS
Authors’ contributions
Planned and designed of the study: Li Y
Searched the literature and wrote the manuscript, performed revisions, read and approved the final
manuscript for publication: Zhang F, Li Y

Availability of data and materials
Not applicable.

Financial support and sponsorship
The present study was supported by the National Natural Science Foundation of China (31770537),
International S & T Cooperation Program of China (ISTCP) (2015DFA31650); International S & T
Cooperation Program of Gansu Province (18YF1WA113).

Conflicts of interest
All authors declared that they have no conflicts of interest.

Ethics approval and consent to participate
Not applicable.