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Takeshi Kuwata



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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-06 - The Link Between Tumor Promoting Fibrous Microenvironment and Immunosuppressive Microenvironment in Stage I Lung Adenocarcinoma (ID 14371)

      12:00 - 13:30  |  Author(s): Takeshi Kuwata

      • Abstract
      • Slides

      Background

      Podoplanin-positive cancer-associated fibroblasts (PDPN (+)CAFs) play an important role in cancer progression in non-small-cell lung cancer (NSCLC). The aim of this study is to clarify the correlation between fibrous microenvironment containing PDPN (+) CAFs and immune microenvironment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      174 cases with stage I primary lung adenocarcinoma were analyzed in this study. We evaluated PDPN (+) CAFs and immune-related cells; CD 204-positive tumor-associated macrophages (CD204 (+) TAMs); CD8-positive T cells; and FOXP3-positive T cells in cancer stroma by immunohistochemical staining method. By analyzing the gene expression profiles of lung adenocarcinoma (n=442), we compared the expression level of immune-regulatory cytokines between PDPN expression-high group and PDPN expression-low group.

      4c3880bb027f159e801041b1021e88e8 Result

      Presence of PDPN (+) CAFs was a risk factor for recurrence (P = 0.012). The number of CD204 (+) TAMs was significantly higher in PDPN (+) CAFs cases than in PDPN (+) CAFs cases (P < 0.001). Furthermore, CD8 (+)/FOXP3 (+) T cell ratio was significantly lower in PDPN (+) CAFs cases (P = 0.027). Within the same tumor, the number of CD 204 (+) TAMs was significantly higher in PDPN (+) CAFs area than in PDPN (-) CAFs area (P < 0.001). Moreover, CD8 (+)/FOXP3 (+) T cell ratio tend to be lower in PDPN (+) CAFs area than in PDPN (+) CAFs area (P = 0.062). Microarray analysis revealed PDPN expression-high group had significant higher levels of M-CSF; a cytokine inducing M2 macrophage polarization, and TGFβ1, IDO, VEGFA and galectin 1; immunosuppressive cytokines.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current results revealed that lung adenocarcinoma with PDPN (+) CAFs is typified by an immunosuppressive microenvironment, suggesting the close link between tumor promoting fibrous microenvironment and immune microenvironment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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