Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens
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Marina K. Baine1, Gabriela Turcu2, Christopher R. Zito1,3, Adebowale J. Adeniran4, Robert L. Camp4, Lieping Chen5, Harriet M. Kluger1,*, Lucia B. Jilaveanu1,*
1Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
2Department of Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
3Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, CT, USA
4Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
5Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
*These authors have contributed equally to this work
Harriet M. Kluger, e-mail: email@example.com
Keywords: tumor infiltrating lymphocytes (TILs), renal cell carcinoma (RCC), primary, metastatic
Received: May 05, 2015 Accepted: June 29, 2015 Published: July 10, 2015
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.
Marina K Baine
Christopher R Zito
Adebowale J Adeniran
Robert L Camp
Harriet M. Kluger
Primary Contact _
Lucia B Jilaveanu
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