Cargando…
NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes
Cancers can escape immunesurveillance by diminishing the expression of MHC class-I molecules (MHC-I) and components of the antigen-processing machinery (APM). Developing new approaches to reverse these defects could boost the efforts to restore antitumor immunity. Recent studies have shown that the...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938303/ https://www.ncbi.nlm.nih.gov/pubmed/27471621 http://dx.doi.org/10.1080/2162402X.2016.1151593 |
_version_ | 1782441839286026240 |
---|---|
author | Rodriguez, Galaxia M. Bobbala, Diwakar Serrano, Daniel Mayhue, Marian Champagne, Audrey Saucier, Caroline Steimle, Viktor Kufer, Thomas A. Menendez, Alfredo Ramanathan, Sheela Ilangumaran, Subburaj |
author_facet | Rodriguez, Galaxia M. Bobbala, Diwakar Serrano, Daniel Mayhue, Marian Champagne, Audrey Saucier, Caroline Steimle, Viktor Kufer, Thomas A. Menendez, Alfredo Ramanathan, Sheela Ilangumaran, Subburaj |
author_sort | Rodriguez, Galaxia M. |
collection | PubMed |
description | Cancers can escape immunesurveillance by diminishing the expression of MHC class-I molecules (MHC-I) and components of the antigen-processing machinery (APM). Developing new approaches to reverse these defects could boost the efforts to restore antitumor immunity. Recent studies have shown that the expression of MHC-I and antigen-processing molecules is transcriptionally regulated by NOD-like receptor CARD domain containing 5 (NLRC5). To investigate whether NLRC5 could be used to improve tumor immunogenicity, we established stable lines of B16-F10 melanoma cells expressing NLRC5 (B16-5), the T cell co-stimulatory molecule CD80 (B16-CD80) or both (B16-5/80). Cells harboring NLRC5 constitutively expressed MHC-I and LMP2, LMP7 and TAP1 genes of the APM. The B16-5 cells efficiently presented the melanoma antigenic peptide gp100(25–33) to Pmel-1 TCR transgenic CD8(+) T cells and induced their proliferation. In the presence of CD80, B16-5 cells stimulated Pmel-1 cells even without the addition of gp100 peptide, indicating that NLRC5 facilitated the processing and presentation of endogenous tumor antigen. Upon subcutaneous implantation, B16-5 cells showed markedly reduced tumor growth in C57BL/6 hosts but not in immunodeficient hosts, indicating that the NLRC5-expressing tumor cells elicited antitumor immunity. Following intravenous injection, B16-5 and B16-5/80 cells formed fewer lung tumor foci compared to control cells. In mice depleted of CD8(+) T cells, B16-5 cells formed large subcutaneous and lung tumors. Finally, immunization with irradiated B16-5 cells conferred protection against challenge by parental B16 cells. Collectively, our findings indicate that NLRC5 could be exploited to restore tumor immunogenicity and to stimulate protective antitumor immunity. |
format | Online Article Text |
id | pubmed-4938303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-49383032016-07-28 NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes Rodriguez, Galaxia M. Bobbala, Diwakar Serrano, Daniel Mayhue, Marian Champagne, Audrey Saucier, Caroline Steimle, Viktor Kufer, Thomas A. Menendez, Alfredo Ramanathan, Sheela Ilangumaran, Subburaj Oncoimmunology Original Research Cancers can escape immunesurveillance by diminishing the expression of MHC class-I molecules (MHC-I) and components of the antigen-processing machinery (APM). Developing new approaches to reverse these defects could boost the efforts to restore antitumor immunity. Recent studies have shown that the expression of MHC-I and antigen-processing molecules is transcriptionally regulated by NOD-like receptor CARD domain containing 5 (NLRC5). To investigate whether NLRC5 could be used to improve tumor immunogenicity, we established stable lines of B16-F10 melanoma cells expressing NLRC5 (B16-5), the T cell co-stimulatory molecule CD80 (B16-CD80) or both (B16-5/80). Cells harboring NLRC5 constitutively expressed MHC-I and LMP2, LMP7 and TAP1 genes of the APM. The B16-5 cells efficiently presented the melanoma antigenic peptide gp100(25–33) to Pmel-1 TCR transgenic CD8(+) T cells and induced their proliferation. In the presence of CD80, B16-5 cells stimulated Pmel-1 cells even without the addition of gp100 peptide, indicating that NLRC5 facilitated the processing and presentation of endogenous tumor antigen. Upon subcutaneous implantation, B16-5 cells showed markedly reduced tumor growth in C57BL/6 hosts but not in immunodeficient hosts, indicating that the NLRC5-expressing tumor cells elicited antitumor immunity. Following intravenous injection, B16-5 and B16-5/80 cells formed fewer lung tumor foci compared to control cells. In mice depleted of CD8(+) T cells, B16-5 cells formed large subcutaneous and lung tumors. Finally, immunization with irradiated B16-5 cells conferred protection against challenge by parental B16 cells. Collectively, our findings indicate that NLRC5 could be exploited to restore tumor immunogenicity and to stimulate protective antitumor immunity. Taylor & Francis 2016-03-28 /pmc/articles/PMC4938303/ /pubmed/27471621 http://dx.doi.org/10.1080/2162402X.2016.1151593 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Original Research Rodriguez, Galaxia M. Bobbala, Diwakar Serrano, Daniel Mayhue, Marian Champagne, Audrey Saucier, Caroline Steimle, Viktor Kufer, Thomas A. Menendez, Alfredo Ramanathan, Sheela Ilangumaran, Subburaj NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title | NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title_full | NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title_fullStr | NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title_full_unstemmed | NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title_short | NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes |
title_sort | nlrc5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to cd8(+) t lymphocytes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938303/ https://www.ncbi.nlm.nih.gov/pubmed/27471621 http://dx.doi.org/10.1080/2162402X.2016.1151593 |
work_keys_str_mv | AT rodriguezgalaxiam nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT bobbaladiwakar nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT serranodaniel nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT mayhuemarian nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT champagneaudrey nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT sauciercaroline nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT steimleviktor nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT kuferthomasa nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT menendezalfredo nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT ramanathansheela nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes AT ilangumaransubburaj nlrc5elicitsantitumorimmunitybyenhancingprocessingandpresentationoftumorantigenstocd8tlymphocytes |