期刊
ONCOTARGET
卷 6, 期 28, 页码 24990-25002出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4572
关键词
tumor infiltrating lymphocytes (TILs); renal cell carcinoma (RCC); primary; metastatic
资金
- NIH [R0-1 CA158167, K24CA172123]
- CTSA Grant from the National Center for Research Resources (NCRR) [KL2 TR000140]
- National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH)
- NIH roadmap for Medical Research
- Lung Cancer research Foundation-LUNGevity and Melanoma Research Alliance [308721]
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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