title: Several immune escape patterns in non-Hodgkin's lymphomas.
abstract: Follicular Lymphomas (FL) and diffuse large B cell lymphomas (DLBCL) must evolve some immune escape strategy to develop from lymphoid organs, but their immune evasion pathways remain poorly characterized. We investigated this issue by transcriptome data mining and immunohistochemistry (IHC) of FL and DLBCL lymphoma biopsies. A set of genes involved in cancer immune-evasion pathways (Immune Escape Gene Set, IEGS) was defined and the distribution of the expression levels of these genes was compared in FL, DLBCL and normal B cell transcriptomes downloaded from the GEO database. The whole IEGS was significantly upregulated in all the lymphoma samples but not in B cells or other control tissues, as shown by the overexpression of thePD-1, PD-L1, PD-L2andLAG3genes. Tissue microarray immunostainings forPD-1, PD-L1, PD-L2andLAG3proteins on additional biopsies from 27 FL and 27 DLBCL patients confirmed the expression of these proteins. The immune infiltrates were more abundant in FL than DLBCL samples, and the microenvironment of FL comprised higher rates of PD-1+lymphocytes. Further, DLBCL tumor cells comprised a higher proportion of PD-1+, PD-L1+, PD-L2+and LAG3+lymphoma cells than the FL tumor cells, confirming that DLBCL mount immune escape strategies distinct from FL. In addition, some cases of DLBCL had tumor cells co-expressing bothPD-1, PD-L1andPD-L2. Among the DLBCLs, the activated B cell (ABC) subtype comprised more PD-L1+and PD-L2+lymphoma cells than the GC subtype. Thus, we infer that FL and DLBCL evolved several pathways of immune escape.
authors.affiliation: Institut Universitaire du Cancer-Oncopole de Toulouse ; Toulouse, France ; Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.affiliation: Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France ; Laboratoire Jean Kuntzmann; CNRS UMR5224 ; Grenoble, France.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Charmpi
authors.affiliation: Institut Universitaire du Cancer-Oncopole de Toulouse ; Toulouse, France ; Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Gravelle
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tosolini
authors.affiliation: Institut Universitaire du Cancer-Oncopole de Toulouse ; Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Franchet
authors.affiliation: Institut Universitaire du Cancer-Oncopole de Toulouse ; Toulouse, France ; Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.affiliation: Institut Universitaire du Cancer-Oncopole de Toulouse ; Toulouse, France ; Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.affiliation: Institut de Recherche Pierre Fabre ; Castres, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bidaut
authors.affiliation: Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France ; Laboratoire Jean Kuntzmann; CNRS UMR5224 ; Grenoble, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ycart
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse; INSERM UMR1037 ; Toulouse, France ; Université Toulouse III Paul-Sabatier ; Toulouse, France ; ERL 5294 CNRS ; Toulouse, France ; Programme Hospitalo-Universitaire en Cancérologie CAPTOR ; Toulouse, France ; Institut Carnot Lymphome CALYM ; Toulouse, France ; Laboratoire d'Excellence 'TOUCAN' ; Toulouse, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
keywords: PD-1/PD-L1 axis; TMA; immune escape; lymphoma; transcriptomes