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Mario Orozco-Morales



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-16 - CD47 Expression and Prognosis in Patients with Small Cell Lung CancerCD47 Expression and Prognosis in Patients with Small Cell Lung Cancer (ID 2935)

      08:00 - 18:00  |  Author(s): Mario Orozco-Morales

      • Abstract

      Background

      CD47 is an integral membrane protein expressed in all cells. CD47 present two opposing roles in cell survival. CD47 can interact with signal-regulatory protein-α (SIRP-a) on macrophages, prevents phagocytic clearance. Besides, CD47 signaling through the thrombospondin-1 limits self-renewal and suppresses expression of the stem cell transcription factors cMyc, Sox2, Oct4, and Klf4 in non-transformed cells. Data on the clinical significance of CD47 expression in patients with small cell lung cancer remain limited.

      Method

      Forty-five naive patients with small cell lung cancer diagnosis were evaluated. Tumor samples obtained by biopsy or surgical resection, were collected for CD47 evaluation. Tumor samples were scored according to the fraction of stained cells at each intensity. The staining intensity of the cell membrane was scored within a scale ranging from 0-3. To determine the prognostic and predictive biomarkers of CD47, patients were stratified according to a cutoff point. This cutoff was optimized as a function of overall survival (OS) using the X-tile and Cutoff Finder software

      Result

      Preliminary results showed that CD47 was present in 26.7% of population. We stratified the CD47 in two cohorts: CD47 positive-negative and a score of CD47>80. The CD47>80 was present mainly in patient with more than 60 years old (35% vs. 8.0%, p=0.024). Longer overall survival was associated with ECOG-PS 0-1 (20.2 vs. 6.9 p=0.001), disease stage IIIB (49.4 vs. 8.0, p=0.020), absent of CNS metastases (14.1-6.8, p=0.016) and absent of pleural effusion (16.2 vs. 6.99, p=0.002). Interestingly, patient with CD47 positive present better OS (10.8 vs. 6.99, p=0.485) but not reaching significance and patient with a score of CD47>80 have better OS (14.0 vs 9.2, p=0.296).

      Conclusion

      Immune checkpoint CD47 expressed on the surface of tumor cells allows them to escape immunosurveillance. We previously reported that high CD47 expression was associated with the presence of somatic EGFR mutations in patients with NSCLC. In these patients, high CD47 expression was an independent prognostic factor of worse progression-free survival. Recent studies have indicated that the signal-regulatory protein (SIRP)α–CD47 pathway regulate a phagocytosis checkpoint in macrophages and other innate immune cells. In contrast, in this report we found that high CD47 expression was associated with <60 years old patient and better overall survival. Previously, studies in small cells lug cancer express high levels of CD47 and the blocking of CD47 enhances phagocytosis inhibits tumor growth. CD47 have a dual role, when interact with SIRPα avoid clearance of cells, but it interacts with thrombospondin 1 inhibits cell cycle progression and induces senescence in endothelial cells. Previous studies have shown that the protein TSP1 is as potent inhibitor of angiogenesis and its antiangiogenic activity is mediated by its receptors, CD36 and CD47. In conclusion CD47 have different function according to the ligand, and is a potential biomarker in cancer