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J. Izzo



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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-066 - Programmed Cell Death Ligand 1 (PD-L1) Overexpression and Low Immune Infiltrate Score Correlate with Poor Outcome in Lung Adenocarcinoma (ID 776)

      09:30 - 09:30  |  Author(s): J. Izzo

      • Abstract

      Background:
      PD-L1 is a key immunoregulatory checkpoint which suppresses cytotoxic immune response in a variety of physiologic and pathologic conditions. Thus, inhibition of PD-L1 can lead to reactivating tumor immunity and assist to cancer therapy. PD-L1 overexpression in the tumor cells has been correlated to a lessened immune response and consequent worse prognosis in a variety of cancers. To better understand the immune profiling of PD-L1 expression and its interplay with immune cells, we analyzed the correlation between image analysis-based immunohistochemical (IHC) expression of PD-L1 and tumor infiltrating immune cells density in surgically resected non-small cell lung carcinomas (NSCLC), and the correlation with clinical and pathological features, including patient outcome.

      Methods:
      IHC for PD-L1, PD-1, CD3, CD4, CD8, CD45RO, CD57, CD68, Granzyme B and FOXP3 were performed in 254 surgical resected stages I-III NSCLC, Adenocarcinoma (ADC=146) and Squamous cell Carcinoma (SqCC=108) from formalin-fixed and paraffin-embedded tissues. PD-L1 membrane expression on tumor cells and density of inflammatory cells were quantified using image analysis in intra-tumoral (IT) and peri-tumoral (PT) compartments. H-score > 5 was used as a cut-off for positive PD-L1 expression and an immune-score (IMS) using CD8/CD4/CD68 was devised. PD-L1 expression and inflammatory cells were correlated with clinico-pathologic features and patient outcomes.

      Results:
      Positive PD-L1 expression was seen in 26.84% (n=69) of the entire cohort, 23.29% (n=34) of 146 ADC and 23.40% (n=35) of 115 SqCC. In ADC, higher levels of PD-L1 expression were detected in tumors with solid histology pattern compared with other histology patterns (P=0.034), and in lifetime smokers compared with non-smokers (P<0.0001). In SqCC PD-L1 expression was positive correlation with tumor size (Rho=0.19471, P=0.0435). In overall, PD-L1 expression correlated positively with inflammatory cell density in both IT and PT compartments in ADC and SqCC. Patients with KRAS mutation (P=0.00058), solid tumor (P<0.0001) or smoker (P = 0.0446) were more likely to have positive PD-L1 expression tumor cells in ADC. No correlation was detected between EGFR mutation and immune markers. Using PD-L1 and CD8/CD4/CD68 IMS expression levels, in ADC and SqCC, we identified 4 groups of tumors (Table 1). Multivariate Cox proportional hazard regression analysis demonstrated that tumors with high PD-L1 expression and low IMS in ADC exhibited significantly poor recurrence-free (HR=4.299; P=0.0101) and overall survival (HR=5.632; P=0.0010).

      Table 1. Summary of the correlation between PD-L1 expression levels and immune-score (IMS=CD8/CD4/CD68) in adenocarcinoma (ADC) and squamous cells carcinoma (SQCC).
      PDL-1 H-score (ADC) IMS (Low) IMS (High) Total
      <5 61 (41.78%) 51 (34.93%) 112 (76.71%)
      ≥5 8 (5.48%) 26 (17.81%) 34 (23.29%)
      Total 69 (47.26%) 77 (52.74%) 146 (100.0%)
      PDL-1 H-score (SqCC)
      <5 37 (34.30%) 36 (33.30%) 73 (67.60%)
      ≥5 17 (15.70%) 18 (16.70%) 35 (32.40%)
      Total 54 (50.00%) 54 (50.00%) 108 (100.0%)


      Conclusion:
      Higher PD-L1 expression is associated with solid pattern in adenocarcinoma and higher level of tumoral immune infiltrate. We developed an immune score which when combined with PD-L1 expression significantly correlates with patient outcome in surgically resected ADCs. (Supported by grants UT-Lung SPORE P50CA70907 and CPRIT RP120713).