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Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific $CD8^{+}$ T Cell Response in Hepatocellular Carcinoma
| Content Provider | MDPI |
|---|---|
| Author | Julia, Peña-Asensio Calvo, Henar Torralba, Miguel Miquel, Joaquín De-Villalobos, Eduardo Sanz- Larrubia, Juan-Ramón |
| Copyright Year | 2021 |
| Description | Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8+ T cells is discussed in this review. |
| Starting Page | 1922 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13081922 |
| Journal | Cancers |
| Issue Number | 8 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-04-16 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Hepatocellular Carcinoma Immunotherapy Pd-1 Pd-l1 Immune Check-point Inhibitor Combination Therapy Cd8 T Cell Response |
| Content Type | Text |
| Resource Type | Article |
