Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

• DOI: 10.18632/oncotarget.5696
• Publication Date: 2015-10-27T11:08:01Z
• Authors: Patrick N. Harter; Simon Bernatz; Alexander Scholz; Pia S. Zeiner; Jenny Zinke; Makoto Kiyose; Stella Blasel; Rudi Beschorner; Christian Senft; Benjamin Bender; Michael W. Ronell...; Harriet Wikman; Markus Glatzel; Matthias Meinhardt; Tareq A. Juratli; Joachim P. Steinbach; Karl H. Plate; Jörg Wischhusen; Benjamin Weide; Michel Mittelbronn
• Keywords: Tumor-infiltrating lymphocytes; Clinical Significance

// Patrick N. Harter 1, 2, 3 , Simon Bernatz 1 Alexander Scholz 4 Pia S. Zeiner 5 Jenny Zinke Makoto Kiyose 6 Stella Blasel Rudi Beschorner 7 Christian Senft 3, 8 Benjamin Bender 9 Michael W. Ronellenfitsch 10 Harriet Wikman 11 Markus Glatzel 12 Matthias Meinhardt 13 Tareq A. Juratli 14 Joachim P. Steinbach Karl H. Plate Jörg Wischhusen 15 Weide 16, 17 Michel Mittelbronn Edinger Institute, Institute of Neurology, University Frankfurt am Main, Germany 2 German Cancer Consortium (DKTK), Heidelberg, Research Center (DKFZ), Laboratory Immunology and Vascular Biology, Stanford School Medicine, Palo Alto, CA, USA Department Neuroradiology, Neuropathology, Tuebingen, Neurosurgery, Senckenberg Neurooncology, Tumor biology, Medical Hamburg-Eppendorf, Hamburg, Pathology, Dresden, Faculty Medicine Hospital Carl Gustav Carus Technische Universität Gynecology, Wuerzburg, 16 Dermatology, Immunology, Correspondence to: Mittelbronn, e-mail: [e-mail] Harter, [e-mail] Keywords: tumor-infiltrating lymphocytes, brain metastases, PD-1, PD-L1 Received: April 21, 2015 Accepted: September Published: October ABSTRACT The activation immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human we aimed at characterizing tumor infiltrating lymphocytes (TILs) expression checkpoints the respective tumors. Two metastases cohorts, a mixed entity cohort ( n = 252) breast carcinoma validation 96) were analyzed CD3+, CD8+, FOXP3+, PD-1+ PD-L1+ immunohistochemistry. Analyses association clinico-epidemiological neuroradiological parameters such as or size performed. TILs infiltrated three different patterns (stromal, peritumoral, diffuse). While carcinomas often show strong stromal infiltration, melanomas diffusely infiltrate Highest levels CD3+ CD8+ seen renal cell (RCC) strongest PD-1 on RCCs melanomas. High amounts TILs, high ratios PD-1+/CD8+ negatively correlated size, indicating that smaller response might get blocked. strongly FOXP3 expression. No significant was observed, while trend towards better melanoma (Log-Rank p 0.0537). In summary, seem to be most immunogenic entities. Differences immunotherapeutic between entities regarding attributable this finding need further investigation larger cohorts.