NUK - logo
E-viri
Recenzirano Odprti dostop
  • Neoadjuvant chemotherapy (N...
    Mesnage, S.J.L.; Auguste, A.; Genestie, C.; Dunant, A.; Pain, E.; Drusch, F.; Gouy, S.; Morice, P.; Bentivegna, E.; Lhomme, C.; Pautier, P.; Michels, J.; Le Formal, A.; Cheaib, B.; Adam, J.; Leary, A.F.

    Annals of oncology, March 2017, 2017-03-01, 2017-03-00, 20170301, Letnik: 28, Številka: 3
    Journal Article

    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 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. 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% versus 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. 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.