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Marjorie G. Zauderer



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    MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD
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      MA12.07 - gC1qR Expression is Independently Prognostic for Survival Benefit Following Chemotherapy in Mesothelioma (Now Available) (ID 13284)

      11:10 - 11:15  |  Author(s): Marjorie G. Zauderer

      • Abstract
      • Presentation
      • Slides

      Background

      Overexpression of gC1qR, a multicompartmental and multifunctional cellular protein, has been shown to promote chemotherapy-induced apoptosis in cancer cells, but compromise CD4 T-cell proliferation in viral infections. The goal of this study was to investigate the overexpression of gC1qR, and its prognostic association with chemotherapy and CD4 T-cell infiltration in malignant pleural mesothelioma (MPM).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays comprising 6 tumoral and 3 stromal cores from 265 patients with MPM (216 epitheloid, 26 biphasic, and 23sarcomatoid, 1989-2010) were investigated by immunohistochemistry for gC1qR expression (intensity and distribution by H-score, range 0-300), and CD4 T-cell infiltration. Overall survival (OS) was analyzed by the Kaplan-Meier method (high versus low gC1qR expression delineated by median score). Multi-variable analysis included clinical, pathological factors and stage (T, N).

      4c3880bb027f159e801041b1021e88e8 Result

      In comparison to benign and reactive mesothelial cells (median H-score 30), gC1qR is overexpressed (median H-score 155) in all histological types of MPMs (263/265, 99.2%). In epithelioid MPM patients – 1) among patients who received neoadjuvant chemotherapy (NAC), high gC1qR was associated with better median OS (25 vs.11 months, Fig1A), 2) among patients without NAC, high gC1qR was associated with better survival, survival benefit is pronounced in patients who received postoperative chemotherapy (median OS 38 vs.19 months, Fig1B), and 3) in multivariate analysis, high gC1qR was an independent factor for better OS. gC1qR expression did not correlate with CD4 T cell infiltration. However, among patients without NAC, high CD4+ T cell infiltration-high gC1qR expression was associated with better OS (26 vs 18,12, and11 months, Fig1C).

      gc1qr.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      gC1qR is overexpressed on MPM cells. MPM patients with high gC1qR expression have a significant survival benefit particularly following chemotherapy; or in the presence of high CD4 T-cell infiltration.

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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-40 - VISTA is Highly Expressed in Malignant Pleural Mesothelioma (MPM) and Independent of PD-L1 Expression (ID 13232)

      16:45 - 18:00  |  Presenting Author(s): Marjorie G. Zauderer

      • Abstract

      Background

      PD-1 blockade is effective in only a minority of MPM patients and predictors of response in MPM are unclear. Recent TCGA analysis of MPM revealed VISTA (V-domain Ig-containing suppressor of T cell activation), another inhibitory T cell checkpoint protein, to be frequently expressed in MPMs. In search of other immunotherapeutic targets in MPM, we evaluated the expression of VISTA, its relationship with expression of PD-L1, and the association with response to PD-1 blockade in MPM.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively interrogated the MPM database at Memorial Sloan Kettering to identify patients who received immune checkpoint inhibitors (ICIs). Archival tissue, where available, was obtained and we performed immunohistochemistry (IHC) using antibodies to PD-L1 (clone E1L3N) and VISTA (clone D1L2G), both from Cell Signaling Technology. Imaging studies were reviewed with a thoracic radiologist according to the modified RECIST criteria.

      4c3880bb027f159e801041b1021e88e8 Result

      37 patients were identified as having received at least one dose of ICI, of whom 26 patients had tissue for VISTA/PD-L1 testing. VISTA was positive (>1%) in 25 (96%) and >50% in 22 (84%). PD-L1 was positive in 11 (42%) and >50% in two (8%). No evident correlation between VISTA and PD-L1 expression was seen. Correlation with response will be reported.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In contrast to PD-L1, VISTA is highly expressed in most patients with MPM. Its expression appears independent of PD-L1 expression. Molecules targeting VISTA and its ligand should be prioritized for clinical development in MPM.

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    WS02 - Mesothelioma Workshop (ID 996)

    • Event: WCLC 2018
    • Type: Workshop
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/23/2018, 08:00 - 11:15, Room 205 AC
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      WS02.15 - Novel Approaches for Targeting BAP1 (Now Available) (ID 14759)

      10:25 - 10:40  |  Presenting Author(s): Marjorie G. Zauderer

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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