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P. Zhang

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    MINI 03 - PD1 Axis Inhibition and EGFR (ID 101)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI03.02 - PD-L1 Displays a Funtional Effect in the Acquired Chemoresistance in Lung Cancer (ID 3187)

      16:45 - 18:15  |  Author(s): P. Zhang

      • Abstract
      • Presentation
      • Slides

      Although neoadjuvant chemotherapy (NAC) for advanced lung cancer can improve operability and local disease control, the duration of benefit is limited before resistance develops. PD-L1, which was a co-stimulatory molecule,interacting with PD-1, has a crucial role in T-cell regulation in immune response. Interest remains in combining chemotherapy and immune therapies to overcome resistance.

      In the study, we used immunohistochemistry, real-time PCR and flow cytometry techniques to investigatethe correlation between overall survival (OS) and disease free survival (DFS) of lung cancer patients and the expression of programmed cell death ligand1 (PD-L1) and the effect of NAC on the expression of PD-L1 in lung cancer cells.

      Firstly, we identified PD-L1 was uprelugated in the SD lung cancer patient by the RNA-seq analysis. Therefore, we performed IHC evaluation in the total 194 patients of NSCLC. The patients with PD-L1 (−) had much better OS compared to those who were PD-L1 (+), and a high PD-L1 expression level in the cancer cells was significantly correlated with a shorter OS and DFS in patients with NAC from the 194 patient (n=78). Meanwhile,in patients who had stable disease (SD) to NAC, there was a rise in the expression of PD-L1, and patients with NAC (n=78) had significantly high rate of positive PD-L1 expression compared with those without NAC (n=116, p= 0.001). The chemotherapy of lung cancer can induce the expression of PD-L1, which may be one of the resistance mechanisms of NAC. Changes in PD-L1 expression were examined in vitro and vivo. Inhibition of the PI3K/AKT pathway reduced the up-regulation of PD-L1 induced by cisplatin, suggesting an involvement of PI3K/AKT pathway in up-regulation of PD-L1.Moreover, knock down of PD-L1 can lead to an increase in apoptosis, as well as cisplatin-induced apoptosis. And caspase7 might play an important role in the apoptosis of lung cancer cells after the knockdown of PD-L1.

      These findings support provide a relationship between PD-L1 expression and chemoresistance. All in all, these results suggest the use of PD-L1 inhibitor with chemotherapy after surgery, in lung cancer patients who received NAC.

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