High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma.

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Date publication

octobre 2023


Blood advances


Membres identifiés du Cancéropôle Est :
Pr MARTIN Laurent, Dr ROSSI Cédric

Tous les auteurs :
Camus V, Viailly PJ, Drieux F, Veresezan EL, Sesques P, Haioun C, Durot E, Patey M, Rossi C, Martin L, Rainville V, Bohers E, Ruminy P, Penther D, Kaltenbach S, Bruneau J, Paillassa J, Tournilhac O, Willaume A, Antier C, Lazarovici J, Leveque E, Decazes P, Becker S, Tonnelet D, Berriolo-Riedinger A, Gaulard P, Tilly H, Molina TJ, Traverse-Glehen A, Jardin F


Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive large B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemorefractory cases with poor outcomes. To identify patients at high risk of chemorefractoriness, we performed molecular characterization of a retrospective multicenter cohort of PMBL patients treated with first-line immunochemotherapy. The traits of the patients with gene-expression profiling (GEP) data (n=120) were as follows: median [range] age of 34 [18-67] years, female sex 58.3%, elevated LDH 82.5%, ECOG 0-1 85.7%, Ann Arbor stage I-II 55%, IPI 1-2 64.4%, and median metabolic tumor volume 290.4 [15.7-1147.5] cm3. Among all 137 markers tested for correlation with survival data, only PDL1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 (30.8%) patients (PDL1high/PDL2high; cutoff: median expression of each gene: PDL1 = 0.402, PDL2 = 9.147). The baseline clinical characteristics of PDL1high/PDL2high patients were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor PFS (HR=4.292, 95% CI [1.447-12.817]) and OS (HR=8.24 [1.71-39.7]). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR= 5.22 [1.352-20.168], OS: HR= 10.368 [1.204-89.267]). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR=6.11 [1.61-23.2]). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poor outcomes from standard chemotherapy who might benefit from first-line anti-PD1 immunotherapy.


Blood Adv. 2023 10 20;: