Τίτλος:
B7-H3 expression in NSCLC and its association with B7-H4, PD-L1 and tumor-infiltrating lymphocytes
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members. Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor-infiltrating lymphocytes (TIL), PD-L1, B7-H4, and major clinicopathologic characteristics is in 3 NSCLC cohorts. Experimental design: We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4, and TILs in 634 NSCLC cases with validated antibodies. Associations between the marker levels, major clinicopathologic variables and survival were analyzed. Results: Expression of B7-H3 protein was found in 80.4% (510/634) of the cases. High B7-H3 protein level (top 10 percentile) was associated with poor overall survival (P < 0.05). Elevated B7-H3 was consistently associated with smoking history across the 3 cohorts, but not with sex, age, clinical stage, and histology. Coexpression of B7-H3 and PD-L1 was found in 17.6% of the cases (112/634) and with B7-H4 in 10% (63/634). B7-H4 and PD-L1 were simultaneously detected only in 1.8% of NSCLCs (12/634). The expression of B7-H3 was not associated with the levels of CD3-, CD8-, and CD20-positive TILs. Conclusions: B7-H3 protein is expressed in the majority of NSCLCs and is associated with smoking history. High levels of B7-H3 protein have a negative prognostic impact in lung carcinomas. Coexpression of B7-H3 with PD-L1 and B7-H4 is relatively low, suggesting a nonredundant biological role of these targets. © 2017 AACR.
Συγγραφείς:
Altan, M.
Pelekanou, V.
Schalper, K.A.
Toki, M.
Gaule, P.
Syrigos, K.
Herbst, R.S.
Rimm, D.L.
Περιοδικό:
Clinical Cancer Research
Εκδότης:
American Association for Cancer Research Inc.
Λέξεις-κλειδιά:
B7 H3 protein; membrane protein; programmed death 1 ligand 1; unclassified drug; V set domain containing T cell activation inhibitor 1; B7 antigen; CD274 protein, human; CD276 protein, human; programmed death 1 ligand 1; tumor marker; V set domain containing T cell activation inhibitor 1; VTCN1 protein, human, aged; Article; cancer prognosis; cancer survival; clinical feature; controlled study; female; histopathology; human; immunofluorescence test; major clinical study; male; non small cell lung cancer; overall survival; priority journal; protein expression; retrospective study; smoking; tumor associated leukocyte; adult; disease free survival; gene expression regulation; genetics; immunohistochemistry; middle aged; non small cell lung cancer; pathology; prognosis; tumor associated leukocyte; tumor cell line, Adult; Aged; B7 Antigens; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Prognosis; V-Set Domain-Containing T-Cell Activation Inhibitor 1
DOI:
10.1158/1078-0432.CCR-16-3107
