Tumour‐infiltrating lymphocytes and expression of programmed death ligand 1 (PD‐L1) in melanoma brain metastases

Media type: E-Article
Title: Tumour‐infiltrating lymphocytes and expression of programmed death ligand 1 (PD‐L1) in melanoma brain metastases
Contributor: Berghoff, Anna Sophie; Ricken, Gerda; Widhalm, Georg; Rajky, Orsolya; Dieckmann, Karin; Birner, Peter; Bartsch, Rupert; Höller, Christoph; Preusser, Matthias
imprint: Wiley, 2015
Published in: Histopathology
Language: English
DOI: 10.1111/his.12537
ISSN: 0309-0167; 1365-2559
Keywords: General Medicine ; Histology ; Pathology and Forensic Medicine
Origination:
Footnote:
Description: <jats:sec><jats:title>Aims</jats:title><jats:p>In this study we aimed to characterize immune infiltrates and expression of programmed death 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐1) and programmed death ligand 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1) in a series of melanoma <jats:styled-content style="fixed-case">BM</jats:styled-content> to provide a basis for experimental therapy using immune checkpoint inhibitors.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>We investigated expression of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1, <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1, <jats:styled-content style="fixed-case">CD</jats:styled-content>3, <jats:styled-content style="fixed-case">CD</jats:styled-content>8, <jats:styled-content style="fixed-case">CD</jats:styled-content>45<jats:styled-content style="fixed-case">RO</jats:styled-content>, forkhead box protein 3 (FoxP3), <jats:styled-content style="fixed-case">CD</jats:styled-content>20 and <jats:styled-content style="fixed-case">BRAF</jats:styled-content> V600E by immunohistochemistry in melanoma <jats:styled-content style="fixed-case">BM</jats:styled-content> samples. Forty‐three specimens [27 of which (62.8%) were <jats:styled-content style="fixed-case">BRAF</jats:styled-content> V600E‐positive] were available. <jats:styled-content style="fixed-case">CD</jats:styled-content>3<jats:sup>+</jats:sup> tumour‐infiltrating lymphocytes (<jats:styled-content style="fixed-case">TIL</jats:styled-content>s) were evident in 33 specimens (76.7%), <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> in 39 (90.7%), <jats:styled-content style="fixed-case">CD</jats:styled-content>45<jats:styled-content style="fixed-case">RO</jats:styled-content><jats:sup>+</jats:sup> in 32 (74.4%), <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1<jats:sup>+</jats:sup> in 27 (62.8%), FoxP3<jats:sup>+</jats:sup> in 21 (48.8%) and <jats:styled-content style="fixed-case">CD</jats:styled-content>20<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">TIL</jats:styled-content>s in 19 (44.2%). Tumour <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression was observed in 22 specimens (51.1%), and in nine of these (40.9%) expression was observed in more than 5% of tumour cells. <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression was associated with higher density of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1<jats:sup>+</jats:sup> (<jats:italic>P </jats:italic>< 0.001), <jats:styled-content style="fixed-case">CD</jats:styled-content>3<jats:sup>+</jats:sup> (<jats:italic>P </jats:italic>=<jats:italic> </jats:italic>0.014) and FoxP3<jats:sup>+</jats:sup> (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001) <jats:styled-content style="fixed-case">TIL</jats:styled-content> infiltration. Density of <jats:styled-content style="fixed-case">CD</jats:styled-content>3<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">TIL</jats:styled-content>s was associated with density of <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001), <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1<jats:sup>+</jats:sup> (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001) and <jats:styled-content style="fixed-case">CD</jats:styled-content>45<jats:styled-content style="fixed-case">RO</jats:styled-content><jats:sup>+</jats:sup> (<jats:italic>P </jats:italic><<jats:italic> </jats:italic>0.001) <jats:styled-content style="fixed-case">TIL</jats:styled-content>s. <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression or <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1<jats:sup>+</jats:sup>, <jats:styled-content style="fixed-case">CD</jats:styled-content>3<jats:sup>+</jats:sup>, <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> or <jats:styled-content style="fixed-case">CD</jats:styled-content>45<jats:styled-content style="fixed-case">RO</jats:styled-content><jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">TIL</jats:styled-content>s density did not correlate with <jats:styled-content style="fixed-case">BRAF</jats:styled-content> V600E status, previous systemic therapy or survival (<jats:italic>P </jats:italic>><jats:italic> </jats:italic>0.05).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Melanoma <jats:styled-content style="fixed-case">BM</jats:styled-content> showed considerable lymphocytic infiltrates and expression of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 in the majority of investigated specimens, with high <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 expression found predominantly in regions of abundant inflammation. Our data indicate that clinical studies should investigate the value of checkpoint inhibitors in patients with melanoma <jats:styled-content style="fixed-case">BM</jats:styled-content>s.</jats:p></jats:sec>

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