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...
Autores principales: | , , , , |
---|---|
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 |