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M. Toki
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-046 - Quantitative Measurement of B7-H3 Protein Expression and Its Association with B7-H4, PD-L1 and TILs in NSCLC (ID 4288)
14:30 - 14:30 | Author(s): M. Toki
- Abstract
Background:
B7-H3 (CD276) is a type I transmembrane protein that belongs to the B7 immunoregulatory family including PD-L1 (B7-H1) and is upregulated in multiple malignancies including Non-Small Cell Lung Cancer (NSCLC). Clinical activity of monoclonal B7-H3 blocking antibodies such as Enoblituzumab are under investigation. In this study we measured the levels of B7-H3 protein in NSCLC and studied its association with major tumor infiltrating lymphocyte (TIL) subsets, levels of PD-L1, B7-H4 and clinico-pathological characteristics in three independent NSCLC cohorts.
Methods:
We used automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3 (clone D9M2L, CST), PD-L1 (clone SP142, Spring), B7-H4 (Clone D1M8I, CST) CD3, CD8 and CD20 in 634 NSCLC cases from 3 retrospective cohorts represented in tissue microarray format. The targets were selectively measured in the tumor and stromal compartments using co-localization with cytokeratin. Associations between the marker levels, major clinic-pathological variables and survival were analyzed.
Results:
Expression of B7-H3 protein was found in 80.4% (510/634) of the cases and the levels were higher in the tumor than in the stromal compartment. High B7-H3 protein expression level (top 10 percentile) was associated with poor survival in two out of three of the cohorts (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. Co-expression 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.
Conclusion:
B7-H3 protein is expressed in the majority of NSCLCs and is associated with smoking history. High B7-H3 protein levels may have a prognostic effect in lung carcinomas. Elevated levels of B7-H3 are not associated with lymphocyte infiltration. Co-expression of B7-H3 with PD-L1 and B7-H4 is relatively low, suggesting a non-redundant biological role of these targets and possibilities for combination therapies using monoclonal antibodies.
