Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8 + T Cell Response in Hepatocellular Carcinoma

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 expr...

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Bibliographic Details
Published in:Cancers 2021-04, Vol.13 (8), p.1922
Main Authors: Peña-Asensio, Julia, Calvo, Henar, Torralba, Miguel, Miquel, Joaquín, Sanz-de-Villalobos, Eduardo, Larrubia, Juan-Ramón
Format: Article
Language:English
Subjects:
Angiogenesis
Antigen presentation
Antigens
Apoptosis
Biopsy
Cancer therapies
CD28 antigen
CD8 antigen
Cell death
Cytokines
Cytotoxicity
Disease resistance
Epigenetics
Gene expression
Growth factors
Hepatitis B
Hepatocellular carcinoma
Immune checkpoint
Immunogenicity
Immunoregulation
Immunotherapy
Inflammation
Liver cancer
Lymphocytes
Lymphocytes T
Medical prognosis
Mutation
Neoantigens
PD-1 protein
PD-L1 protein
Recovery of function
Review
T cell receptors
Tumors
Viruses
Wound healing
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13081922