%0 Journal Article 
%A Peña Asensio, Julia
%A Calvo Sánchez, Henar
%A Torralba González de Suso, Miguel
%A Miquel Plaza, Joaquín
%A Sanz de Villalobos, Eduardo
%A Larrubia Marfil, Juan Ramón
%T Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.
%D 2021
%@ 2072-6694
%U http://hdl.handle.net/10017/50894
%X 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.
%K Hepatocellular carcinoma
%K Immunotherapy
%K PD-1
%K PD-L1
%K Immune check-point inhibitor
%K Combination therapy
%K CD8 T cell response
%K Medicina
%K Medicine
%~ Biblioteca Universidad de Alcala