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Li Zhang



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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-02 - Targeting Established Lung Cancer Through Combination of DNT Cellular Therapy with PD1 Checkpoint Blockade (ID 13046)

      16:45 - 18:00  |  Author(s): Li Zhang

      • Abstract

      Background

      Lung cancer is the leading cause of cancer-related deaths worldwide. Immune-checkpoint blockade such as anti-PD1 therapies achieved clinical benefit which correlated with presence of immune cells in tumors. Adoptive T cell therapies is another form of immunotherapy with therapeutic-potentials, but obtaining sufficient tumor-antigen specific T cells and discovery of high-expressing tumor-specific antigens remain as challenge. Recently, we have demonstrated that a population of cytotoxic T cells (CD3+CD4-CD8-), termed double negative T (DNT) cells, has potent anti-cancer effect in vitro and in patient-derived xenograft models, can be expanded ex vivo to a therapeutic quantity and quality. In this study, whether DNT cell can target established lung cancer either alone or in combination with anti-PD1 is investigated.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Infiltrating T cell populations from 12 resected lung tumors were characterized and compared to resected adjacent and normal tissues using Flow-cytomtery. To determine the efficacy of ex vivo DNT cell therapy on lung cancer, NSG mice subcutaneously engrafted with H460 were systemically infused with DNT cells or DNT cell with Nivolumab in three doses when tumor size reached 100mm3, the tumor size and DNT cell infiltration level were monitored.

      4c3880bb027f159e801041b1021e88e8 Result

      The frequency of DNT cell was reduced in lung tumor when compared to the adjacent and non-tumoral tissues of the same patient. Like conventional CD4 and CD8 T cells, 36%-52% of DNT cells within tumor expressed elevated levels of PD1, suggesting that DNT cells function may be suppressed by PD-1 pathway in patients. Using xenograft mice, we show that treatment with DNT cell alone reduced tumor growth by 14%-38%. A greater reduction (30%-68%) was observed when DNT cell treatment was combined with PD1 blockade, where PD1 blockade alone had no significant effect. Compared to DNT cell transfer alone, DNT cells with PD1 blockade led to a greater infiltration of cells with higher expression of cytotoxicity markers NKG2D and IFN-y and reduced inhibitory markers TIM3 and LAG3.

      8eea62084ca7e541d918e823422bd82e Conclusion

      These studies indicate the potential of DNT cell for the treatment of established lung cancer and that combination of DNT cell with PD1 blockade may further enhance the treatment efficacy by increasing DNT cell infiltrating to solid tumor.

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      P1.04-05 - Elucidating the Role of Leukocyte-Associated Immunoglobin-Like Receptor 2 (LAIR2) in Lung Cancer Development (ID 13859)

      16:45 - 18:00  |  Author(s): Li Zhang

      • Abstract

      Background

      The tumor microenvironment play an important role in shaping cancer development. The contexture of stromal infiltrates have been shown promote or inhibit tumor growth and patient prognosis. In attempts to gain insight into the immune networks that regulate tumorigenesis, we used genome wide expression datasets from patients with resected early stage non-small cell lung cancer (NSCLC) to identify immune-related genes associated with patient survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Gene expression analysis was conducted on microarray datasets from 128 early-stage NSCLC adenocarcinoma resected tumor samples. Limiting analysis to immune-related genes, we identified a minimum gene set containing LAIR2 that was prognostic for lung adenocarcinoma. Immunohistochemistry and gene ontology analysis were used to determine the function of LAIR2.

      4c3880bb027f159e801041b1021e88e8 Result

      From the gene signature, the gene encoding the immune collagen receptor LAIR2, was highly expressed within the high-risk patient subgroup (HR = 2.71, 95% CI = 1.49 to 4.90, P = 0.001). Gene ontology analysis revealed that LAIR2 expression correlated with negative immune regulation and associated immune signatures. Immunohistochemistry of resected lung adenocarcinoma revealed heterogeneous expression of LAIR2 within tumor epithelium and stromal immune cells, suggesting specificity and localization. ELISA for LAIR2 suggest that CD4+ Th2 cells maybe a major source of LAIR2 secretion and that recombinant LAIR2 may promote T cell exhaustion by activation of CD8+ T cells and upregulation of PD1 and LAG3.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that expression of LAIR2 result in poor patient prognosis and is associated with negative immune regulation. An understanding of LAIR2 function will provide insight into factors required during lung cancer progression and targets for intervention.

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