Abstract 1291
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract
1707 - Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (EPOC1702)
Presenter: Keisuke Kirita
Session: Poster Display session 3
Resources:
Abstract
3594 - Tumor mutation burden (TMB), PD-L1, IFN-γ signaling identify subgroups of patients (pts) who benefit from durvalumab (D, anti-PDL1) or D and tremelimumab (T, anti-CTLA4) treatment in urothelial bladder cancer (UC)
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
744 - The decrease of TMB, TNB and HLA expression are the Mechanism of Drug Resistance of NSCLC to immunosuppressive PD-1/PD-l1.
Presenter: Sheng Yu
Session: Poster Display session 3
Resources:
Abstract
2350 - Eosinophilia during treatment of immune checkpoint inhibitors (ICIs) predicts succeeding onset of immune-related adverse events (irAEs)
Presenter: Rika Kizawa
Session: Poster Display session 3
Resources:
Abstract
5930 - A transcriptomic immunologic signature predicts favorable outcome in neoadjuvant chemotherapy treated triple negative breast tumors.
Presenter: Javier Pérez-peña
Session: Poster Display session 3
Resources:
Abstract
6127 - Alterations of TMB and TCR repertoires during Chemotherapy in East Asian lung cancer patients without TKI-related driver gene mutations
Presenter: Lele Song
Session: Poster Display session 3
Resources:
Abstract
1310 - Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi-PD-1 antibody.
Presenter: Motoo Nomura
Session: Poster Display session 3
Resources:
Abstract
2286 - Extracellular matrix and tissue derived metabolites in a liquid biopsy identifies endotypes of metastatic melanoma patients with differential response to immune checkpoint inhibitor treatment
Presenter: Nicholas Willumsen
Session: Poster Display session 3
Resources:
Abstract
4107 - Pathologic scoring of pre-treatment H&E biopsies predicts overall survival in patients with metastatic clear cell renal cell carcinoma receiving nivolumab monotherapy
Presenter: Julie Stein
Session: Poster Display session 3
Resources:
Abstract