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Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does no...

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Autores principales: Baine, Marina K., Turcu, Gabriela, Zito, Christopher R., Adeniran, Adebowale J., Camp, Robert L., Chen, Lieping, Kluger, Harriet M., Jilaveanu, Lucia B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694809/
https://www.ncbi.nlm.nih.gov/pubmed/26317902
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author Baine, Marina K.
Turcu, Gabriela
Zito, Christopher R.
Adeniran, Adebowale J.
Camp, Robert L.
Chen, Lieping
Kluger, Harriet M.
Jilaveanu, Lucia B.
author_facet Baine, Marina K.
Turcu, Gabriela
Zito, Christopher R.
Adeniran, Adebowale J.
Camp, Robert L.
Chen, Lieping
Kluger, Harriet M.
Jilaveanu, Lucia B.
author_sort Baine, Marina K.
collection PubMed
description Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease.
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spelling pubmed-46948092016-01-20 Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens Baine, Marina K. Turcu, Gabriela Zito, Christopher R. Adeniran, Adebowale J. Camp, Robert L. Chen, Lieping Kluger, Harriet M. Jilaveanu, Lucia B. Oncotarget Research Paper Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. Impact Journals LLC 2015-07-10 /pmc/articles/PMC4694809/ /pubmed/26317902 Text en Copyright: © 2015 Baine et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Baine, Marina K.
Turcu, Gabriela
Zito, Christopher R.
Adeniran, Adebowale J.
Camp, Robert L.
Chen, Lieping
Kluger, Harriet M.
Jilaveanu, Lucia B.
Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title_full Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title_fullStr Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title_full_unstemmed Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title_short Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
title_sort characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694809/
https://www.ncbi.nlm.nih.gov/pubmed/26317902
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