Cargando…

Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy

With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have pioneered revolutionary immunotherapies for malignancies. But most patients struggled to respond to anti-PD owing to primary or acquired resistance or even hyperprogression, pointing to more efforts needed to e...

Descripción completa

Detalles Bibliográficos
Autores principales: Long, Yiru, Yu, Xiaolu, Chen, Runqiu, Tong, Yongliang, Gong, Likun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157498/
https://www.ncbi.nlm.nih.gov/pubmed/35663968
http://dx.doi.org/10.3389/fimmu.2022.910704
_version_ 1784718650727464960
author Long, Yiru
Yu, Xiaolu
Chen, Runqiu
Tong, Yongliang
Gong, Likun
author_facet Long, Yiru
Yu, Xiaolu
Chen, Runqiu
Tong, Yongliang
Gong, Likun
author_sort Long, Yiru
collection PubMed
description With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have pioneered revolutionary immunotherapies for malignancies. But most patients struggled to respond to anti-PD owing to primary or acquired resistance or even hyperprogression, pointing to more efforts needed to explore this axis. PD-1 constrains T-cell immunoreactivity via engaging with PD-L1 of tumor/myeloid cells is the canonical PD-1/PD-L1 axis function mode. Studies are increasingly aware of the impact of noncanonical PD-1/PD-L1 expression in various cancers. PD-L1 induced on activated T-cells ligates to PD-1 to mediate self-tolerance or acts on intratumoral myeloid cells and other T-cells, affecting their survival, differentiation and immunophenotyping, leading to tumor immunosuppression. Myeloid PD-1 interferes with their proliferation, differentiation, cytokine secretion and phagocytosis, mediating remarkable pro-tumor effects. Tumor cell intrinsic PD-1 signaling has diverse functions in different tumors, resulting in pro-proliferation or proliferation inhibition. These nonclassical PD-1/PD-L1 functions may be novel anti-PD mechanisms or causes of treatment resistance. This review highlights the nonnegligible role of T-cell-intrinsic PD-L1 and tumor/myeloid PD-1 in the cell interplay network and the complex impact on the efficacy of anti-PD antibodies. Reconsidering and rational utilization of the comprehensive PD-1/PD-L1 axis could cumulate breakthroughs in precision treatment and combination for anti-PD therapies.
format Online
Article
Text
id pubmed-9157498
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91574982022-06-02 Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy Long, Yiru Yu, Xiaolu Chen, Runqiu Tong, Yongliang Gong, Likun Front Immunol Immunology With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have pioneered revolutionary immunotherapies for malignancies. But most patients struggled to respond to anti-PD owing to primary or acquired resistance or even hyperprogression, pointing to more efforts needed to explore this axis. PD-1 constrains T-cell immunoreactivity via engaging with PD-L1 of tumor/myeloid cells is the canonical PD-1/PD-L1 axis function mode. Studies are increasingly aware of the impact of noncanonical PD-1/PD-L1 expression in various cancers. PD-L1 induced on activated T-cells ligates to PD-1 to mediate self-tolerance or acts on intratumoral myeloid cells and other T-cells, affecting their survival, differentiation and immunophenotyping, leading to tumor immunosuppression. Myeloid PD-1 interferes with their proliferation, differentiation, cytokine secretion and phagocytosis, mediating remarkable pro-tumor effects. Tumor cell intrinsic PD-1 signaling has diverse functions in different tumors, resulting in pro-proliferation or proliferation inhibition. These nonclassical PD-1/PD-L1 functions may be novel anti-PD mechanisms or causes of treatment resistance. This review highlights the nonnegligible role of T-cell-intrinsic PD-L1 and tumor/myeloid PD-1 in the cell interplay network and the complex impact on the efficacy of anti-PD antibodies. Reconsidering and rational utilization of the comprehensive PD-1/PD-L1 axis could cumulate breakthroughs in precision treatment and combination for anti-PD therapies. Frontiers Media S.A. 2022-05-18 /pmc/articles/PMC9157498/ /pubmed/35663968 http://dx.doi.org/10.3389/fimmu.2022.910704 Text en Copyright © 2022 Long, Yu, Chen, Tong and Gong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Long, Yiru
Yu, Xiaolu
Chen, Runqiu
Tong, Yongliang
Gong, Likun
Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title_full Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title_fullStr Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title_full_unstemmed Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title_short Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy
title_sort noncanonical pd-1/pd-l1 axis in relation to the efficacy of anti-pd therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157498/
https://www.ncbi.nlm.nih.gov/pubmed/35663968
http://dx.doi.org/10.3389/fimmu.2022.910704
work_keys_str_mv AT longyiru noncanonicalpd1pdl1axisinrelationtotheefficacyofantipdtherapy
AT yuxiaolu noncanonicalpd1pdl1axisinrelationtotheefficacyofantipdtherapy
AT chenrunqiu noncanonicalpd1pdl1axisinrelationtotheefficacyofantipdtherapy
AT tongyongliang noncanonicalpd1pdl1axisinrelationtotheefficacyofantipdtherapy
AT gonglikun noncanonicalpd1pdl1axisinrelationtotheefficacyofantipdtherapy