SMOLY : Phenotype and Functions of Monocyte Subtypes in High Grade B Lymphoma: Towards New Biomarkers?

Primary objective :

Describe and compare the distribution of the different monocytic subpopulations according to the chemosensitivity profile (group 1) or chemoresistance (group 2) of patients with DLBCL and healthy donors (group 3), and identify their specific functionalities.

Secondary objective :

To determine the prognostic impact in terms of progression-free survival (EFS) of the distribution of the monocytic sub-population (s) defined i during the primary objective, in a retrospective study (BMS Ly Trans)

Design/Methodology : Retrospective, observational, monocentric study.

• - Part 1: Phenotypic and functional study of monocytic sub - populations of patients with DLBCL.

• Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy.

Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment.

Group 3: 15 healthy patients.

A - Irish Lab (Nashville)

• Phenotypic analysis by mass cytometry: This new technology allows the integration of multiple data with membrane markers, intracytoplasmic proteins as well as transcription factors, thus providing global modeling of signaling pathways

B - UMR 917 (Rennes) 8 months Cell sorting: The four subtypes of monocytes described above will be sorted by flow cytometry according to the expression of CD14, CD16 and Slan.

• High-throughput transcriptional analysis: cell lysis and real-time PCR in order to study the expression of genes involved in the mechanisms of immunomodulation.Bio-informatics, Integrated analysis: The set of clinical, transcriptomic and proteomic data will be analyzed in an integrated way using tools and algorithms working within the Irish lab.
• - 2nd part (Rennes) - 6 months : Populations differentially expressed between groups in part 1 will be analyzed on a cohort of 100 samples. These parameters will be analyzed jointly after integration in a database, uni- and multivariate analysis and the survival probability will be calculated for groups with a log-rank test.

Expected benefits :

• - To allow a better understanding of the monocyte compartment in DLBCL, particularly with regard to the immunosuppressive capacity of some of these cellular subtypes.
• - To refine the interest of the biomarker "monocyte level" on EFS in patients with DLBCL, highlighting the monocyte subtype involved.
• - To continue the collaboration between the two sites, which will allow to combine technologies and expertise present in Rennes (patient recruitment, cell sorting, molecular analysis (Biomark)) or in Nashville (CyTOF, bioinformatics, integrated analysis).

Inclusion criteria

• Age> or equal to 18 years and <or equal to 70 years
• Large cell diffuse NHL B (WHO)
• Stage I - II bulky with tumor mass> 7cm or stage III or IV of the Ann Arbor classification
• No prior treatment (even corticosteroid therapy)
• HIV negative
• Informed consent signed
• Patient follow-up> 2 years after completion of first-line treatment

Exclusion criteria

• Age <18 years or> 70 years
• Aggressive transformation of a known low-grade NHL
• Primary CNS Lymphoma
• MALT transformed lymphoma or Burkitt's lymphoma
• Lymphoma post transplantation
• Stage I or II with tumor mass <or equal to 7cm
• Cancer with the exception of carcinoma in situ of the cervix or non-invasive cutaneous epithelium
• History of cured cancer treated systematically and / or causing secondary complications in the six months prior to inclusion in the protocol
• Pre-treatment
• HIV positive
• Patient with a disability who does not have a good understanding of informed consent
• Unsigned informed consent
• Patient follow-up <2 years after completion of first-line treatment