PD-L1 expression is associated with clinical benefit from anti-PD1/anti-PD-L1 therapies in advanced NSCLC. However, additional biomarkers are needed to predict which patients will benefit most. The aim of this study is to correlate specific genomic alterations with immunological biomarkers in a cohort of NSCLC.
Patients diagnosed with NSCLC from 2000 to 2005 were retrospectively reviewed. Genetic mutations and copy number of selected genes were determined by Sanger and FISH. Immunophenotype was defined by PD-L1, HLA-1 and TILs CD8+ immunostaining and scored as follows: PD-L1 positivity ≥ 5% on membrane tumor cells; HLA-1 intensity: 0+,1+,2+; TILs CD8+ score: low or high infiltration. Statistical analysis using Chi-square test and logistic regression were performed.
From 150 patients: 87% males; stage: 90% I-II, 10% III-IV; histology: 42% adenocarcinoma (ADC), 44% squamous (SCC), 14% sarcomatoid carcinoma (SaC). Genomic alterations according to histologic subtype are summarized in table 1. PD-L1 was positive in 47% of tumors (49% of ADC, 43% of SCC, 58% of SaC), and correlated with TILs CD8+ (p <.001) and HLA-1 (p=.002). PD-L1 positivity was associated with MET alterations (4.5% MET amp, 2% METexon14 skipping), OR=5.4 (1.4-21.2), p=.015. ADC harbouring STK11 loss of function were correlated with negative PD-L1 (p = .01) and associated with immunosupressive phenotype (negative PD-L1, low CD8+), OR=11.6 (2.1-64), p=.005. Distinct PD-L1 expression was evidenced in KRAS mutant tumors according to additional co-mutations: 25% of KRAS+STK11 were PD-L1+ whereas 75% of KRAS+TP53 were PD-L1+, despite no statistically significance.
|ADC||n= 59 (100%)||SCC||n= 62 (100%)||SaC||n=19 (100%)|
|mut (exons 2-3)||14 (20%)||GA||3 (5%)||Mut||1 (5%)|
|wt||45 (80%)||NC||53 (85%)||wt||16 (94%)|
|Unknown||6 (10%)||Unknown||2 (1)|
|mut (exon18-21)||6 (10)||Mut||0||Mutation||4 (21)|
|wt||49 (83)||wt||58 (94)||wt||12 (63)|
|Unknown||4 (7)||Unknown||4 (6)||Unknown||3 (16)|
|Transloc.||1 (2)||GA||6 (10)||Mutation||1 (5)|
|wt||57(96)||NC||20 (32)||wt||15 (79)|
|Unknown||1 (2)||Unknown||36 (58)||Unknown||3 (16)|
|mut||10 (17)||Amp||9 (15)|
|wt||46 (78)||NA||51 (82)|
|Unknown||3 (5)||Unknown||2 (3)|
MET and STK11 alterations were correlated with differential expression of tumor PD-L1. STK11 mutant tumors were more likely to have an immunosupressive phenotype. Tumors harbouring specific genomic alterations might be enriched for distinct immunophenotypes which might contribute to rational use of immunotherapies.