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Pei Wang



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    MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA02.09 - Prognostic Impact of Immune Cell Biomarkers in Surgically Resectable Non-Small Cell Lung Cancer (Now Available) (ID 2646)

      10:30 - 12:00  |  Author(s): Pei Wang

      • Abstract
      • Presentation
      • Slides

      Background

      Immune cells within the tumor microenvironment (TME) play an important role in the development, progression and eventual outcomes of non-small cell lung cancer (NSCLC). The relative balance of immune effector and regulatory cell subpopulations may tilt the TME to be either detrimental or supportive of tumorogenesis and will have a profound impact on the tumor’s eventual destiny. In early-stage lung cancer, the role of individual immune cell subtypes in the TME on survival outcomes following surgical resection is unknown.

      Method

      This project made use of The Cancer Genome Atlas (TCGA) Program data. We computed sample-specific scores for different immune cells using xCell, a new model for estimating different immune cell types from RNAseq data, for all stage I-IIIA NSCLCs. Then, we assessed the association between each cell type and survival with Cox Regression, while adjusting for important clinical variables (i.e., stage, age, gender, smoking status). We stratified the analysis according to histological subtype.

      Result

      There were 910 surgically resected early-stage NSCLC analyzed, of which 438 were adenocarcinomas (LUADs) and 472 were squamous cell (LUSC) samples. Higher levels of natural killer cells, neutrophils, and mast cells within tumors were associated with significantly improved survival in LUAD patients, whereas no immune cell type was associated with survival for LUSC patients or the combined analysis.

      Figure 1: Adjusted Survival According to Estimated Immune Cell Infiltration

      figure 1 adjusted survival according to estimated immune cell infiltration.png

      Hazard ratios are adjusted for stage, gender, age and smoking status

      Conclusion

      Innate and adaptive immune cells within the TME may have prognostic value in early-stage NSCLC patients undergoing surgical resection. However, the role of individual immune cells may vary according to histological subtype. Prospective research should continue to assess the association of the immune cell composition of the TME with clinical outcomes.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-14 - Prognostic Value of Immune Cell Biomarkers in Surgically Resectable Non-Small Cell Lung Cancer: A Meta-Analysis (Now Available) (ID 2658)

      09:45 - 18:00  |  Author(s): Pei Wang

      • Abstract
      • Slides

      Background

      Immune cells within the tumor microenvironment (TME) play an important role in the development, progression and outcomes of non-small cell lung cancer (NSCLC). We conducted the first meta-analysis of studies assessing the role of individual immune cells in surgically resected stage I-III NSCLC to evaluate the prognostic value of immune cell biomarkers.

      Method

      PubMed was searched to identify eligible studies assessing clinical outcomes of surgically resected stage I-III NSCLC patients according to immune cell subsets: CD3+ T cells, CD4+ T Helper cells, CD8+ T cytotoxic cells, CD20+ B cells, FoxP3+T Regulatory cells, Natural Killer cells (CD56/CD57+), macrophages (CD68+), and Mast Cells. Meta-analysis was performed using a linear mixed-effects model to determine overall survival (OS) and disease free survival (DFS), and was reported according to whether or not the study adjusted for clinical covariates. I2 was used to assess heterogeneity across studies.

      Result

      42 articles (7,906 patients) were included in this analysis. Higher levels of CD20+ B cells were associated with better OS, while increased FoxP3+ T regulatory cells and Mast Cells were associated with worse OS in unadjusted studies. However, in studies adjusting for clinical variables, CD8+ T cytotoxic cells and Natural Killer cells were also found to be associated with improved OS, while mast cells no longer were significantly detrimental. CD20+ B cells were associated with better DFS in unadjusted studies; in adjusted studies, CD8+ T cytotoxic cells were associated with better survival and FoxP3+ T Regulatory cells were associated with worse survival, with CD20+ B cells no longer significantly associated survival. I2 did not show substantial heterogeneity between studies.

      Table 1: Meta-Analysis Survival Estimates

      OS

      DFS

      Biomarker

      Unadjusted HR (95% CI)

      N, Heterogeneity (%)

      Adjusted HR

      (95% CI)

      N, Heterogeneity (%)

      Unadjusted HR (95% CI)

      N, Heterogeneity (%)

      Adjusted HR

      (95% CI)

      N, Heterogeneity (%)

      CD3+

      T cells

      0.98

      (0.87-1.12)

      6 articles

      I2= 0.00

      0.71

      (0.37-1.37)

      3 articles

      I2= 0.00

      0.98

      (0.86-1.12)

      5 articles

      I2= 0.00%

      -------

      -------

      CD4+

      T Helper cells

      0.64

      (0.37-1.10)

      4 articles

      I2= 13.65

      0.80

      (0.50-1.28)

      4 articles

      I2= 0.00

      0.72

      (0.39-1.32)

      3 articles

      I2= 0.00%

      0.59

      (0.11-3.12)

      1 article

      CD8+

      T Cytotoxic cells

      0.99

      (0.95-1.04)

      14 articles

      I2= 0.00

      0.71

      (0.52-0.96)

      12 articles

      I2= 20.95

      0.94

      (0.77-1.16)

      8 articles

      I2= 16.65%

      0.60

      (0.41,-0.87)

      9 articles

      I2= 20.43%

      CD20+

      B cells

      0.45

      (0.22-0.93)

      5 articles

      I2= 52.29

      0.16

      (0.04-0.64)

      1 article

      0.57

      (0.33,-1.00)

      4 articles

      I2= 0.00%

      0.51

      (0.20-1.32)

      1 article

      FoxP3+

      T Regulatory cells

      1.78

      (1.20-2.64)

      9 articles

      I2= 14.93

      2.38

      (1.56-3.65)

      6 articles

      I2= 0.00

      1.45

      (0.81-2.59)

      3 articles

      I2= 0.00%

      2.07

      (1.10-3.90)

      3 articles

      I2= 0.00%

      Natural Killer cells

      0.66

      (0.35-1.25)

      3 articles

      I2= 13.63

      0.50

      (0.26-0.95)

      4 articles

      I2= 0.00

      1.35

      (0.39-4.66)

      1 article

      0.59

      (0.27-1.28)

      2 articles

      I2= 0.00%

      Macrophages

      1.11

      (0.65-1.90)

      5 articles

      I2= 18.11

      1.04

      (0.69-1.55)

      6 articles

      I2= 0.00

      -------

      -------

      1.88

      (0.87-4.08)

      4 articles

      I2= 43.97%

      Mast Cells

      1.81

      (1.01-3.15)

      3 articles

      I2=0.00

      2.01

      (0.88-3.92)

      3 articles

      I2=43.99

      2.30

      (1.20-4.70)

      1 article

      1.50

      (0.60-3.60)

      1article

      HR= Hazard Ratio, CI = Confidence Interval

      Conclusion

      Immune cell subsets are able to provide prognostic information in early-stage NSCLC undergoing surgical resection. When evaluating these immune biomarkers, adjustment for clinical covariates can have a profound impact on survival estimates.

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