RT info:eu-repo/semantics/article
T1 Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.
A1 Peña Asensio, Julia
A1 Calvo Sánchez, Henar
A1 Torralba González de Suso, Miguel
A1 Miquel Plaza, Joaquín
A1 Sanz de Villalobos, Eduardo
A1 Larrubia Marfil, Juan Ramón
K1 Hepatocellular carcinoma
K1 Immunotherapy
K1 PD-1
K1 PD-L1
K1 Immune check-point inhibitor
K1 Combination therapy
K1 CD8 T cell response
K1 Medicina
K1 Medicine
AB Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class geneticsignature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Thosepotential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens oraberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cellsexpress the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) whichimpairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that givesrise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmittedto the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumorresistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop otherfailures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-basedcombinatory 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.
SN 2072-6694
YR 2021
FD 2021-04-16
LK http://hdl.handle.net/10017/50894
UL http://hdl.handle.net/10017/50894
LA eng
NO Peña-Asensio, J.; Calvo, H.; Torralba, M.; Miquel, J.; Sanz-de-Villalobos, E.; Larrubia, J.-R. Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma. Cancers 2021, 13, 1922.
NO Instituto de Salud Carlos III
DS MINDS@UW
RD 29-abr-2024