Author of

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  MA11 - Biomarkers of IO Response (ID 912)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Immunooncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD

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    MA11.02 - Increased CD3+ TIL Infiltration and Low FOXP3+/CD8+ TIL Ratio Can Predict Anti-PD-1 Therapeutic Response in Non-Small Cell Lung Cancer Patients (ID 12553)

    10:35 - 10:40  |  Author(s): Yeon Bi Han
    • Abstract
    • Presentation
    • Slides

    Background
    

    To determine whether distinct tumor microenvironments differentially affect the clinical response to anti-PD-1 therapy in non-small cell lung cancer (NSCLC), we investigated the expression level of PD-L1 and tumor infiltrating lymphocytes (TILs) and elucidate their predictive role.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Forty pretreated specimens (including 21 resected and 19 biopsied tissues) from 36 advanced, treatment-refractory NSCLC patients who underwent PD-1 blockade therapy were analyzed. PD-L1 expression by tumor cells and the distribution of CD3, CD8, CD4, FOXP3 and PD-1 positive TILs were immunohistochemically assessed. The mean number of cells positive for each marker in covered total fields was expressed in density per mm² using digital image analyzer. In addition, CD8+/CD3+, CD8+/CD4+, FOXP3+/CD8+, and PD-1+/CD8+ ratios were calculated for each specimen using the mean number of total fields.

    4c3880bb027f159e801041b1021e88e8 Result
    

    CD3+ and CD8+ TILs were distributed more in PD-L1 positive group compared to PD-L1 negative group. Inversely, EGFR mutant group showed fewer CD3+ TILs than EGFR-naïve group. The patients in the clinical benefit group with PD-1 blockade showed a higher number of CD3+, CD8+ TILs and a higher CD8+/CD3+ TIL ratio (p=0.003, p=0.001, and p =0.042) and a lower FOXP3+/CD8+ TIL ratio compared to non-responders (p=0.001). We analyzed the effects of TIL, PD-L1 and clinicopathologic factors in PD-1 blockade therapeutic response using logistic regression. In multivariate analysis, increased CD3+ TIL infiltration and low FOXP3+/CD8+ TIL ratio were found to be independent predictors of clinical benefit with PD-1 blockade. (p=0.014 and p=0.03, respectively). Using receiver operating characteristic curves, levels of CD3+ TIL and FOXP3+/CD8+ TIL ratio that provide the best distinguishing point between responder versus non-responder to PD-1 blockade were 617.5/mm² and 25%, respectively (p=0.007 and p=0.003). Considering that 1 mm² is about 5 high power fields (HPF), a good response to the PD-1 blockade can be expected when CD3 + TIL is observed in 120 per 1 HPF and CD8 + TIL : FOXP3 + TIL are greater than 4 : 1. In addition, there were no difference between sample acquisition method (resection vs. biopsy) and duration (3, 6, and 12 months before PD-1 blockade treatment), and TIL expression.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Based on our results, TIL is an independent predictive factor of response to PD-1 blockade and we suggested a cutoff value of TIL to predict responder group. In addition, properly sampled small biopsy tissue and well preserved archival specimens are feasible to evaluate TIL status.

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