Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC)
Menée à l'aide de trois lignées cellulaires et à partir d'échantillons tumoraux fixés au formol ou à l'alcool-formol acétique après prélèvement sur 150 patientes atteintes d'un cancer épithélial de l'ovaire, cette étude met en évidence une augmentation de la concentration de lymphocytes et de l'expression de PD-L1 dans la tumeur après une chimiothérapie néoadjuvante
Background : Lymphocytic infiltration at diagnosis is prognostic in EOC, however the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described.
Patients and Methods : Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining.
Results : sTILs were detected in all tumours at diagnosis (range 2%-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N=83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P=0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% vs 18% for PFI <6 months, P=0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P=0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P=0.02 and HR 0.60, P=0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected.
Conclusions : In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.
Annals of Oncology , résumé, 2015