Author of

• 17629

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  P2.03b - Poster Session with Presenters Present (ID 465)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17718

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    P2.03b-089 - CD1C in Lung Adenocarcinoma: Prognosis and Cellular Origin (ID 4809)

    14:30 - 14:30  |  Author(s): D. Ly
    • Abstract

    Background:
    Adaptive immune response is critical for cancer surveillance and elimination. Dendritic cells (DC) arise from a hematopoietic lineage distinct from other leukocytes which play a central role in adaptive immunity. CD1C is expressed in DC, presenting exogenous lipid antigens to T cell receptor to activate “unconventional” T cells. This study aims to evaluate the cellular expression and prognostic value of CD1C.
    
    Methods:
    The study used 5 gene expression datasets: UHN181 [lung adenocarcinoma (ADC, n=128), squamous cell carcinoma (SqCC, n=43)], GSE30219 (ADC n=81, non-ADC n=138)], and 3 integrated cohorts [non-SqCC NSCLC (n=1106), PRECOG (39 types of cancer, n=~18,000), and TCGA (33 types of cancer, n=11,000)]. Cancer Cell Line Encyclopedia (CCLE) data were used to determine if CD1C was expressed by cancer cell lines. CIBERSORT algorithm was used to estimate immune cell fraction and Cox proportional model was used to evaluate the association of CD1C expression with survival. Immunohistochemistry (IHC) was used to measure protein expression of CD1C.
    
    Results:
    Except for hematopoietic and lymphoid cancer cell lines, all CCLE cell lines lack CD1C expression. CIBERSORT analysis together with Pearson correlation analyses on the ADC cases in UHN181, the integrated cohort, and GSE30219 showed that CD1C was expressed by DC. IHC showed staining with a dendritic cell shape pattern. However, the staining of CD1C did not overlapped with CD11c staining, suggesting a specific DC subtype. Cox proportional regression revealed that CD1C was significantly prognostic in the UHN181 ADC cohort (HR=0.75, p=0.05) as the training set. When CD1C expression was categorized into 3 equal groups, the risk of death was reduced in high compared to low CD1C expression group (HR=0.55, 95%CI 0.28-1.07, p=0.07). CD1C is protective only in PD-L1 low expression group (n=108, HR=0.37, 95%CI 0.15-0.89, p=0.026). The favorable prognosis associated with CD1C expression was validated in the integrated cohort of non-SqCC NSCLC (HR=0.55, 95% CI 0.43-0.72, p<0.0001), and in GSE30219 ADC cohort (HR=0.30, 95% CI 0.11-0.84, p=0.02). In PRECOG and TCGA datasets, high CD1C expression is significantly good prognostic in all cancer types (p<1×10[-7] and p<0.001, respectively), suggesting a universal protective role of CD1C expression in cancers. CD1C IHC score was highly correlated with CD1C mRNA expression in ADC patients of UHN181 and was prognostic (HR=0.46, 95%CI 0.22-0.96, p=0.039).
    
    Conclusion:
    CD1C preferentially is expressed on a subset of DCs and higher expression of CD1C is significant protective factor in all cancer types, especially in lung adenocarcinoma