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L. Amler



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    ORAL 13 - Immunotherapy Biomarkers (ID 104)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL13.03 - Spatiotemporal Effects on Programmed Death Ligand 1 (PD-L1) Expression and Immunophenotype of Non-Small Cell Lung Cancer (NSCLC) (ID 1609)

      16:45 - 18:15  |  Author(s): L. Amler

      • Abstract
      • Slides

      Background:
      PD-L1 is one of the immune-checkpoint molecules that regulates Th1 immune responses and mediates cancer immune evasion. PD-L1 can be expressed on tumor cells (TC) or tumor-infiltrating immune cells (IC) and expression in both cell types can negatively regulate T-cell function in the tumor microenvironment. The goal of this study was to evaluate the intra-patient heterogeneity and temporal changes in PD-L1 expression and overall immune phenotype in NSCLC using paired synchronous and metachronous tumor specimens.

      Methods:
      Thirty-nine patients (pts) with NSCLC treated at Memorial Sloan Kettering Cancer Center were evaluated as part of an IRB approved project. Most were former/current smokers (n=30, 77%) and had adenocarcinoma histology (n=36, 92%). 17 pts were KRAS mutant (45%), and 5 were EGFR mutant (13%). Paired synchronous samples were collected from 17 pts with stage IIIA-N2 resected primary lung and metastatic lymph node (met LN) tissue. Paired metachronous samples were collected from 23 pts (including one patient also with synchronous tissue) with at least two metachronous primary/metastatic (n=14) or metastatic/metastatic tissues (n=9). In pts with metachronous samples, 14 (61%) had systemic intercurrent anti-cancer therapy and 9 (39%) had none. PD-L1 expression was assessed by IHC (clone SP142) on TC and IC. CD8 expression was evaluated by IHC using the C8/144 clone. In addition, expression of ~600 immune genes was analyzed by iChip.

      Results:
      Twenty-five out of 39 tissue pairs were evaluable by PD-L1 IHC (14/17 synchronous, 11/23 metachronous). Among pts with synchronous samples, in the primary tumor, PD-L1 was expressed in <1% of TC or IC in 6 pts, in 1-4% of cells in 5 pts, and in ≥5% of cells in 3 pts. Among those with metachronous samples, in the first collected sample, the PD-L1 expression in <1% of TC or IC was detected in 6 pts, in 1-4% of cells in 2 pts, and in ≥5% of cells in 3 pts. PD-L1 expression was similar across all paired tissues. PD-L1 status at the TC or IC 5% cut-off remained unchanged in all evaluable paired specimens and at the TC or IC 1% cut-off remained unchanged in 80% (11/14 synchronous and 9/11 metachronous) pairs. In both synchronous and metachronous samples, CD8 expression was also similar across paired specimens. The median inter-sample difference in CD8+ T-cell infiltration was 0.5% (95% CI: -0.6% - 3.4%) in synchronous pairs; three pts had a difference >5%. In metachronous pairs, the median difference was -0.4% (95% CI: -1.4% - 0.1%); one pt had a >5% change in CD8+ T-cell infiltration.

      Conclusion:
      In this study, there was a high agreement in PD-L1 expression and CD8+ T-cell infiltration in both paired synchronous and metachronous NSCLC specimens. The low intra-patient heterogeneity of PD-L1 and CD8 expression in this study suggests any available tissue (e.g. primary or met) may be reliable to assess these markers in NSCLC. Overall immune characterization by gene expression analysis in paired tumor specimens will be presented.

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