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F. Rea



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    PD-L1 expression and tumor microenvironment in advanced lung cancer (ID 59)

    • Event: ELCC 2018
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      78O - Immune microenvironment of small cell lung cancer (SCLC): Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumor infiltrating lymphocytes (ID 370)

      16:45 - 18:15  |  Author(s): F. Rea

      • Abstract
      • Presentation
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      Background:
      SCLC represents one of the most aggressive lung malignancies, characterized by a high growth fraction and early metastatic spread. New therapeutic options are badly needed and immunotherapy might represent a promising approach. Unfortunately, so far, no molecular prognostic markers have been validated for clinical practice and data on immune microenvironment are limited.

      Methods:
      We have retrospectively analyzed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 (22C3 clone, DAKO) was performed on tumor cells (TCs) and on tumor-infiltrating lymphocytes (TILs): positivity was defined as PD-L1 expression on 1% or more TCs or TILs. Immunohistochemistry for CD8 (C8/144B clone, DAKO) and FOXP3 (236A/E7 clone, ABCAM) was also performed. A semiquantitative score was used and CD8 and FOXP3 TILs categorized as positive versus negative.

      Results:
      The analysis included 104 patients: 48 surgically resected, 18 patients treated with radical-intent chemo-radiotherapy and 38 metastatic. In overall study population, PD-L1 was expressed in TCs in 25% of cases. The expression of PD-L1 was significantly correlated with stage disease (32% stage I-III; 13% metastatic stage; p:0.034 for TCs and p:0.002 for TILs) and with outcome: median OS 46.8 months (m) (95% CI: 22.6 to 71.0) versus (vs) 10.9 m (95% CI: 6.2 to 15.7; p = 0.047) PD-L1 positive vs negative respectively; the relation with outcome however, was not confirmed in multivariate analysis. CD8-positive TILs and FOXP3-positive TILs were present in 59% and 72% of samples respectively. Neither the presence of CD8+ TILs nor that of FOXP3+ TILs was correlated to stage. The presence of FOXP3-positive TILs was associated with improved prognosis among non-metastatic patients: median OS 52.5 m (95% CI: 21.4 to 83.7) vs 20.5 m (95% CI: 0 to 49.2; p = 0.027) FOXP3-positive vs negative TILs, a relation confirmed in multivariate analysis.

      Conclusions:
      Expression of PD-L1 is reduced in advanced stage SCLC patients. Further studies are needed to understand if down-regulation of PD-L1 is linked to a more aggressive phenotype. The prognostic role of FOXP3 TILs in stage I-III SCLCs warrants further confirmation in larger series of patients.

      Clinical trial identification:


      Legal entity responsible for the study:
      Istituto Oncologico Veneto (IOV), Padua, Italy

      Funding:
      Università degli Studi di Padova

      Disclosure:
      All authors have declared no conflicts of interest.

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