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E. John Wherry



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-02 - Effect of Chemotherapy, Chemoimmunotherapy, and Immunotherapy on Parameters of T Cell Exhaustion in Metastatic Non-Small Cell Lung Cancer (ID 1880)

      10:15 - 18:15  |  Author(s): E. John Wherry

      • Abstract

      Background

      The pharmacodynamic immune response to anti-PD-1 immunotherapy can be tracked in the peripheral blood of cancer patients and is associated with response to therapy. However, it is unclear how chemotherapy and chemoimmunotherapy affect T cell activity. Given the established role of these treatments in Non-Small Cell Lung Cancer (NSCLC), we sought to compare the impact of chemotherapy, chemoimmunotherapy, and immunotherapy on T cell immunity.

      Method

      We prospectively collected blood samples in pts beginning chemotherapy, chemoimmunotherapy, or immunotherapy for metastatic NSCLC at baseline and with each cycle. Peripheral blood mononuclear cells were stained for immune markers and analyzed using 26 parameter flow cytometry. Immune response was characterized by increased expression of Ki67 on PD-1 expressing CD8 T cells. Statistical analysis was performed using paired t-test or Wilcoxon matched pairs analysis based on normality of data. All patients had CT scans with full RECIST 1.1 and tumor volume measurements.

      Result

      We analyzed 28 pts (63% female, median age = 65.5). 9 pts received chemotherapy, 12 pts immunotherapy, and 7 pts chemoimmunotherapy. Both immunotherapy (p = 0.001) and chemoimmunotherapy (p=0.016) resulted in an immune response that peaked at 3 weeks compared to baseline (Figure). No immune response was identified with chemotherapy (p=0.734). Immune response was detected in exhausted T cells (PD1+CD39+ CD8) for both immunotherapy (p =0.007) and chemoimmunotherapy (p =0.031). In addition, chemoimmunotherapy induced activation of CD27+CCR7+ memory CD8 T cells (p=0.0313), not seen with immunotherapy (p= 0.871). figure 1 wclc abstract.jpg

      Conclusion

      Chemoimmunotherapy and immunotherapy, but not chemotherapy, induced a significant immune response in the peripheral blood, peaking at 3 weeks. While immunotherapy and chemoimmunotherapy both targeted an exhausted population, chemoimmunotherapy induced an immune response in exhausted and memory T cells. We have collected more samples, and at time of the WCLC will present these data, as well as correlation with RECIST responses.