PD-L1 expression in uncommon EGFR-mutant non-small cell lung cancer and its response to immunotherapy

Abstract

Background: The efficacy of immunotherapy treating EGFR-positive non-small cell lung cancer (NSCLC) patients has been proved to be limited. However, a series of mutant-patients could be benefit from PD-1 blockade. Therefore, this study evaluated the immune microenvironment in NSCLC with uncommon EGFR mutation, and explored the prospect of immunotherapy in this cohort. Method(s): We retrospectively evaluated the expression of PD-L1, CD4 and CD8 in NSCLC patients who harbored uncommon EGFR mutation at Zhejiang Cancer Hospital between April 2016 and September 2017. The association with clinical factors and outcomes were also explored, as well as the effectiveness of immunotherapy in uncommon mutation-positive cases. [Figure presented] Result: Among the 600 NSCLC patients with EGFR mutation, we retrospectively collected 49 (8.2%) cases bearing uncommon mutation. In total, 49.0% (24/49) of NSCLC patients showed a strong PD-L1 expression in tumor cells, which was significantly higher than common sensitive (19del and L858R) or negative EGFR mutation (49.0% vs 12.1% vs 26.3%, respectively, P<0.05). Furthermore, positive PD-L1 expression was associated with a significantly shortened OS when compared with the negative PD-L1 expression (20.0 vs 44.3 months, P=0.006). And PD-L1 positivity was predominantly observed among patients with high CD8 expression rather than low cases (72.0% vs 25.0%, P=0.001). Notably, we found PD-L1 and CD8 dual-positive cases demonstrated the worst prognosis (OS: 19.3[dual-positive] vs 31.1[single-positive] vs 44.3[dual-negative] months, P=0.023). Additionally, this approach revealed PD-L1 and CD8 positivity were not associated with the response to EGFR-TKIs, playing no role in the de novo resistance of EGFR-TKIs among the uncommon mutated patients. Finally, one patient harboring EGFR G719A mutation with PD-L1 and CD8 dual positivity experienced a favorable response to anti-PD-1 therapy. Conclusion(s): This study revealed the expression of PD-L1, CD4 and CD8 in uncommon EGFR-mutated NSCLC patients. The findings indicated the reshaping of an inflamed immune phenotype characterized by PD-L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to PD-1 blockade. Keywords: EGFR, Immunotherapy, PD-L1Copyright © 2019