PD-L1 immunohistochemistry (IHC) correlates only moderately with response to nivolumab treatment. Characterizing PD-1, PD-L1 and T-cell markers in both tumor and stroma might improve the predictive value of tissue IHC as predictive biomarker in this setting.
From 08-2015 to 12-2016 patients with stage IV NSCLC treated with nivolumab were registered and prospectively followed. A histological tumor biopsy, obtained before start of nivolumab, was required. Tumor PD-L1 expression and immune cell (IC) PD-L1, PD-1, CD3, CD4 and CD8 expression in tumor and stroma was assessed using IHC on serial sections. IC infiltration was scored semi-quantitatively indicating no, very low, low, intermediate, or high infiltration. Presence of CD4+ macrophages in between tumor cells was used to aid assessment of tumor PD-L1 expression. Nivolumab was dosed 3 mg/kg Q2W and response assessment was done by CT every six weeks.
Overall response rate of pts (n = 65) was 23% and quantifiable (≥1%) tumor PD-L1 expression was found in 25% of pts, versus 50%) and associated response rates of 17%, 22% and 57% respectively. Stromal IC expression of PD-L1, CD3, CD4 and CD8 also correlated with response (p
A clear positive correlation was found between PD-L1 expression and response. The distribution of PD-L1 expression was lower compared to historical data. Availability of CD4 IHC that identified PD-L1 positive macrophages is the explanation for lower percentage of tumor PD-L1 positive samples. Stromal PD-L1, CD3, CD4 and CD8 IC expression were all predictive for treatment response. In tumor PD-L1 negative pts, high stromal PD-L1 and/or CD3 IC expression selected pts with a remarkably high response rate.
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Legal entity responsible for the study
A. J. de Langen
VU University Medical Center, Department of Pulmonology
All authors have declared no conflicts of interest.