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Hyun Jung Kwon



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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): Hyun Jung Kwon

      • 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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