Author of

• 17398

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  P2.01 - Poster Session with Presenters Present (ID 461)

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

  • 17476

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    P2.01-078 - Frequent High TIM-3 (HAVCR2) Expression in Resected NSCLC Specimens, Most Notably in Adenocarcinoma Histology (ID 5400)

    14:30 - 14:30  |  Author(s): M. Velez
    • Abstract

    Background:
    Approved anti-programmed cell death-1 (PD-1) therapies have produced durable responses in advanced non-small cell lung cancer (NSCLC), but objective response rates in unselected populations remain modest at approximately 20%. As a result, therapies targeting other immune checkpoints are currently being investigated as monotherapy or in combination with anti-PD-1 therapy. One such immune checkpoint is T-cell immunoglobulin and mucin-domain containing 3 (TIM-3), which is involved in T-cell exhaustion and has also been found on NSCLC tumor cells, more frequently in adenocarcinoma. The present study sought to further characterize the expression of TIM-3 in resected NSCLC specimens via microarray analysis.
    
    Methods:
    Gene expression microarray analysis was performed using the Agilent Whole Human Genome 4x44K 2-color platform for 319 NSCLC and 15 normal lung resection specimens. The reference sample was an equal mixture of 258 of the NSCLC samples included in the study. Microarray data was imported into Rosetta Resolver for analysis. Samples with expression significantly greater than the reference level were classified as high, samples with expression unchanged from the reference were classified as moderate, and samples with significantly lower levels were classified as low (P<0.01). Relationships between TIM-3 expression and smoking status, histology, T stage, and gender were evaluated with the chi-square test. The three survival curves based on TIM-3 expression were compared and a single p-value based on chi-square test was determined using Statistica 13.0.
    
    Results:
    Within the 319 NSCLC tissue samples, 90 samples (28%) had high TIM-3 expression, 150 samples (47%) had moderate expression, and 79 samples (25%) had low expression. Interestingly, 47% (7/15) of normal lung samples evidenced high TIM-3 expression, while none had low TIM-3 expression. Tumors with adenocarcinoma histology had a greater percentage of samples with high TIM-3 expression, 34%, compared to those with squamous cell histology, 17% (p=0.03). Gender and T stage were not significantly related to TIM-3 expression level, while a trend towards high TIM-3 levels was observed in smokers compared to non-smokers (p=0.10). In this surgical cohort, TIM-3 expression did not appear to be prognostic for survival.
    
    Conclusion:
    Our findings suggest that high TIM-3 expression occurs frequently in resected NSCLC, supporting the ongoing evaluation of anti-TIM-3 therapy in NSCLC. Additionally, TIM-3 expression was more frequently high in adenocarcinoma, normal lung, and a trend towards high expression was noted in smokers. Future efforts will focus on identifying cell type specific TIM-3 expression via immunohistochemistry analysis and selecting patients for anti-TIM-3 clinical trials.