title: Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC).
abstract: Brain metastases (BM) are frequent in small cell lung cancer (SCLC). Novel insights into their pathobiology are needed for development of better therapies. We investigated tumor-infiltrating lymphocyte (TIL) subsets (CD3+, CD8+, CD45RO+, FOXP3+ and PD-1+) and expression of PD-L1 in a series of 32 SCLC BM specimens and four matched primary tumor specimens using immunohistochemistry. 30/32 (93.8 %) BM specimens showed TIL infiltration. CD3+ TILs were observed in 30/32 (93.8 %) BM specimens, CD8+ TILs in 25/32 (78.1 %), CD45RO+ TILs in 15/32 (46.9 %), FOXP3+ TILs in 15/32 (46.9 %) and PD-1+ TILs in 1/32 (3.1 %) BM specimens. Patients with infiltration of CD45RO+ TILS had a significantly longer median survival time (11 months; 95 % CI 0.000-26.148) as compared to patients without the presence of CD45RO+ TILs (5 months; 95 % CI 0.966-9.034; p = 0.007; log rank test). Membranous PD-L1 on tumor cells was observed in 24/32 (75.0 %) BM specimens, with 11/32 (34.4 %) cases showing PD-L1 expression in over 5 % of viable BM tumor cells. PD-L1 expression on TILs was seen in 8/32 (25.0 %) and on tumor infiltrating macrophages in 9/32 (28.1 %) cases. Patients with PD-L1 expression on TILs presented with improved survival prognosis (6 versus 29 months; p = 0.002; log rank test). Among matched primary tumors, all (4/4; 100 %) specimens showed TIL infiltration, while PD-L1 expression found in only 1/4 (25.0 %) specimen. TIL infiltration and PD-L1 expression are commonly found in SCLC BM and presence of CD45RO+ memory T-cells and PD-L1+ TILs in SCLC BM seem to associate with favorable survival times. Our data suggest an active immune microenvironment in SCLC BM that may be targetable by immune-modulating drugs.
authors.affiliation: Department of Medicine I and Comprehensive Cancer Center CNS Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Ricken
authors.affiliation: Department for Radiology and Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wilhelm
authors.affiliation: Department of Medicine I and Comprehensive Cancer Center CNS Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rajky
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.|Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Department of Radiotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.affiliation: Department of Medicine I and Comprehensive Cancer Center CNS Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.affiliation: Department of Medicine I and Comprehensive Cancer Center CNS Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. matthias.preusser@meduniwien.ac.at.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000378:metabolism; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000473:pathology*; D012907:Smoking; D013223:Statistics as Topic; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins
keywords: Brain metastases; Immune checkpoint inhibitor; PD-L1 expression; Small cell lung cancer; Tumor infiltrating lymphocytes