Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment

被引:262
作者
D'Angelo, Sandra P. [1 ,2 ]
Shoushtari, Alexander N. [1 ]
Agaram, Narasimhan P. [3 ]
Kuk, Deborah [4 ]
Qin, Li-Xuan [4 ]
Carvajal, Richard D. [2 ,5 ]
Dickson, Mark A. [1 ,2 ]
Gounder, Mrinal [1 ,2 ]
Keohan, Mary Louise [1 ,2 ]
Schwartz, Gary K. [6 ]
Tap, William D. [1 ,2 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, Sarcoma Serv, New York, NY 10065 USA
[2] Weill Cornell Med Coll, New York, NY 10065 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10065 USA
[5] Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma & Immunotherapeut Serv, New York, NY 10065 USA
[6] Columbia Univ Med Ctr, Dept Med, New York, NY 10032 USA
关键词
Sarcoma; Immunotherapy; PD-1; PD-L1; Tumor infiltrating lymphocyte CD3+; CD4+; CD8+; FOXP3+; POTENTIAL MECHANISM; B7-H1; CELLS; CANCER; EXHAUSTION;
D O I
10.1016/j.humpath.2014.11.001
中图分类号
R36 [病理学];
学科分类号
100103 [病原生物学];
摘要
The prognostic and predictive implications of programmed death-ligand 1 (PD-L1) is unknown in sarcoma. We sought to examine the immune milieu in sarcoma specimens. We evaluated PD-L1 expression by immunohistochemistry in sarcoma specimens and quantified tumor-infiltrating lymphocytes (TIL). We correlated expression with clinical parameters and outcomes. Fifty sarcoma patients treated at Memorial Sloan Kettering Cancer Center were selected. Using the DAKO PD-L1 immunohistochemistry assay and archival formalin-fixed paraffin-embedded tissue specimens; PD-L1 expression was examined. Macrophage and lymphocyte PD-L1 status was determined qualitatively. TIL was quantified. Associations between PD-L1 expression in tumor, macrophages and lymphocytes, TIL and clinical-pathological characteristics were performed. The median age was 46 years (range, 22-76), and 66% of patients were men. Tumor, lymphocyte and macrophage PD-L1 expression was noted in 12%, 30% and 58%, respectively, with the highest prevalence in gastrointestinal stromal tumors (29%). Lymphocyte and macrophage infiltration was present in 98% and 90%, respectively. There was no association between clinical features, overall survival and PD-L1 expression in tumor or immune infiltrates. Lymphocyte and macrophage infiltration is common in sarcoma, but PD-L1 tumor expression is uncommon in sarcoma with the highest frequency observed in gastrointestinal stromal tumors. There was no association between PD-L1 expression, TIL and clinicopathological features and overall survival; however, this is limited by the heterogenous patient sample and minimal death events in the studied cohort. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:357 / 365
页数:9
相关论文
共 24 条
[1]
Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients [J].
Baitsch, Lukas ;
Baumgaertner, Petra ;
Devevre, Estelle ;
Raghav, Sunil K. ;
Legat, Amandine ;
Barba, Leticia ;
Wieckowski, Sebastien ;
Bouzourene, Hanifa ;
Deplancke, Bart ;
Romero, Pedro ;
Rufer, Nathalie ;
Speiser, Daniel E. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (06) :2350-2360
[2]
Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido [J].
Balachandran, Vinod P. ;
Cavnar, Michael J. ;
Zeng, Shan ;
Bamboat, Zubin M. ;
Ocuin, Lee M. ;
Obaid, Hebroon ;
Sorenson, Eric C. ;
Popow, Rachel ;
Ariyan, Charlotte ;
Rossi, Ferdinand ;
Besmer, Peter ;
Guo, Tianhua ;
Antonescu, Cristina R. ;
Taguchi, Takahiro ;
Yuan, Jianda ;
Wolchok, Jedd D. ;
Allison, James P. ;
DeMatteo, Ronald P. .
NATURE MEDICINE, 2011, 17 (09) :1094-U99
[3]
Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8+ T-lymphocyte infiltration and affect tumour progression [J].
Berghuis, Dagmar ;
Santos, Susy J. ;
Baelde, Hans J. ;
Taminiau, Antonie H. M. ;
Egeler, R. Maarten ;
Schilham, Marco W. ;
Hogendoorn, Pancras C. W. ;
Lankester, Arjan C. .
JOURNAL OF PATHOLOGY, 2011, 223 (03) :347-357
[4]
Brennan MF, 2012, MANAGEMENT SOFT TISS
[5]
Paradoxical roles of the immune system during cancer development [J].
de Visser, KE ;
Eichten, A ;
Coussens, LM .
NATURE REVIEWS CANCER, 2006, 6 (01) :24-37
[6]
Dong HD, 1999, NAT MED, V5, P1365
[7]
Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
[8]
PISCES: A Horoscope for First-Line Targeted Therapy of Metastatic Renal Cell Carcinoma Reply [J].
Escudier, Bernard ;
Porta, Camillo ;
Powles, Thomas ;
Eisen, Tim ;
Sternberg, Cora N. ;
Mehmud, Faisal ;
Cella, David .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (33)
[9]
The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis [J].
Gooden, M. J. M. ;
de Bock, G. H. ;
Leffers, N. ;
Daemen, T. ;
Nijman, H. W. .
BRITISH JOURNAL OF CANCER, 2011, 105 (01) :93-103
[10]
Herbst R. S., 2013, J CLIN ONCOL S, V31, pa3000