Cargando…
Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer
Background: Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified. Methods: The mRNA expre...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299558/ https://www.ncbi.nlm.nih.gov/pubmed/34307455 http://dx.doi.org/10.3389/fmolb.2021.686803 |
_version_ | 1783726293295038464 |
---|---|
author | Cai, Dongli Wang, Fang Wang, Changgang Jin, Liping |
author_facet | Cai, Dongli Wang, Fang Wang, Changgang Jin, Liping |
author_sort | Cai, Dongli |
collection | PubMed |
description | Background: Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified. Methods: The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of VTCN1 (encoding B7S1) in OvCa were analyzed. The molecular interaction network, Gene Ontology (GO) analysis and Gene set enrichment analysis (GSEA) were used to functionally annotate and predict signaling pathways of VTCN1 in OvCa. Moreover, 32 treatment-naïve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed. Results: B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. VTCN1 expression was significantly correlated with the mRNA expression levels of several other co-inhibitory immune checkpoints. B7S1 protein was found to be highly expressed in CD45(+)CD68(+) myeloid cells, whereas its putative receptor was expressed in CD8(+) tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8(+) TILs. Functional annotations indicated that VTCN1 was involved in regulating T cell-mediated immune responses and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer. Conclusion: In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8(+) TILs, which could be targeted for cancer immunotherapy. |
format | Online Article Text |
id | pubmed-8299558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82995582021-07-24 Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer Cai, Dongli Wang, Fang Wang, Changgang Jin, Liping Front Mol Biosci Molecular Biosciences Background: Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified. Methods: The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of VTCN1 (encoding B7S1) in OvCa were analyzed. The molecular interaction network, Gene Ontology (GO) analysis and Gene set enrichment analysis (GSEA) were used to functionally annotate and predict signaling pathways of VTCN1 in OvCa. Moreover, 32 treatment-naïve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed. Results: B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. VTCN1 expression was significantly correlated with the mRNA expression levels of several other co-inhibitory immune checkpoints. B7S1 protein was found to be highly expressed in CD45(+)CD68(+) myeloid cells, whereas its putative receptor was expressed in CD8(+) tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8(+) TILs. Functional annotations indicated that VTCN1 was involved in regulating T cell-mediated immune responses and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer. Conclusion: In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8(+) TILs, which could be targeted for cancer immunotherapy. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8299558/ /pubmed/34307455 http://dx.doi.org/10.3389/fmolb.2021.686803 Text en Copyright © 2021 Cai, Wang, Wang and Jin. 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 | Molecular Biosciences Cai, Dongli Wang, Fang Wang, Changgang Jin, Liping Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title | Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title_full | Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title_fullStr | Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title_full_unstemmed | Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title_short | Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer |
title_sort | phenotypic and functional analyses of b7s1 in ovarian cancer |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299558/ https://www.ncbi.nlm.nih.gov/pubmed/34307455 http://dx.doi.org/10.3389/fmolb.2021.686803 |
work_keys_str_mv | AT caidongli phenotypicandfunctionalanalysesofb7s1inovariancancer AT wangfang phenotypicandfunctionalanalysesofb7s1inovariancancer AT wangchanggang phenotypicandfunctionalanalysesofb7s1inovariancancer AT jinliping phenotypicandfunctionalanalysesofb7s1inovariancancer |