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# Identification of CD39 as a new therapeutic target in non-Hodgkin's lymphomas

L Rimailho, C Faria, F Gava, P Gravelle, M Tosolini, C Rossi, C Laurent, C Bezombes

► To cite this version:

L Rimailho, C Faria, F Gava, P Gravelle, M Tosolini, et al.. Identification of CD39 as a new therapeutic target in non-Hodgkin's lymphomas. Journées de l’Ecole Doctorale BSB 2023, 2023, Toulouse, France. inserm-04827786

HAL Id: inserm-04827786

https://inserm.hal.science/inserm-04827786v1

Submitted on 10 Dec 2024

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# Identification of CD39 and CD73 as new therapeutic targets in non-Hodgkin's lymphomas

Léa Rimailho*, C Faria, F Gava, P Gravelle, M Tosolini, C Rossi, C Laurent and C Bezombes

Follicular lymphoma (FL) and diffuse large cell B-cell lymphoma (DLBCL) are the two most common
subtypes of non-Hodgkin's lymphomas (NHL) whose treatment has benefited from the introduction
of the anti-CD20 monoclonal antibody Rituximab (RTX) used in combination with chemotherapy.
However, a significant fraction of patients does not respond and all patients relapse. The
identification of mechanisms of resistance to therapies represents a major challenge. In this context,
my team characterized a specific immuno-escape signature (IE) of NHL involving the expression of 54
genes among them, CD39 and CD73, two ectonucleotidases playing a key role in the adenosine
pathway. In the literature, it has been shown that CD39 and CD73 are highly expressed in FL and
DLBCL biopsies and that the level of tumor infiltrating lymphocytes (TILs) expressing CD73 correlates
with a worse prognosis in DLBCL. Moreover, CD39+ expressing TILs in FL appear more abundant
compared to reactive lymph nodes and reflect their hyporesponsiveness. Finally, it has been shown
that TCR stimulation induced CD39 expression in normal γδT lymphocytes, and that tumors
expressing CD39 are more resistant in vivo to RTX. Thus, we hypothesize that TIL expressing
CD39/CD73 in FL and DLBCL could correspond to γδT cells and that their targeting may provide
therapeutical benefit by improving the efficacy of anti-lymphomatous treatment. We are currently
exploring the role of CD39 based on in vitro (NHL cell lines co-cultured with γδT cells) and ex vivo
患者的 lymphoma spheroids) experiments and evaluate if CD39 targeting by a
pharmacological inhibitor improves antibody-dependent cell cytotoxicity in presence of RTX.
Moreover, by using public transcriptomics analysis we are currently exploring the influence of
ENTPD1 (CD39 encoding gene) on NHL survival. Altogether, we expect to identify CD39 and/or CD73
as potential new therapeutic target in FL/DLBCL, diseases that are still considered as incurable.