Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.
AuthorsPeña Asensio, Julia; Calvo Sánchez, Henar; Torralba González de Suso, Miguel; Miquel Plaza, Joaquín; Sanz de Villalobos, Eduardo; [et al.]
IdentifiersPermanent link (URI): http://hdl.handle.net/10017/50894
Instituto de Salud Carlos III
European Regional Development Fund (ERDF)
Gilead Fellowship Programme
Cancers, 2021, v. 13, n. 8, p. 1922
Immune check-point inhibitor
CD8 T cell response
Description / Notes
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.
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ PI19%2F00206/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD14%2F00217 (JRL)/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD16/00014 (JRL)/ES/
© 2021 by the authors. Licensee MDPI
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
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.
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