Tissue Immune Landscape of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation (TIL-GVHD)

Context :

Chronic Graft versus Host Disease (cGVHD) represents the main cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (alloSCT), occurring in 30 and 60%. Translational studies showed that different alloreactive T cell subsets were involved and associated with cGVHD, and regulatory subsets were deficient. Several homeostatic abnormalities of B cell subsets were also shown, which, in the context of high BAFF level, contributed to autoreactive B cell clone emergence.

In alloSCT patients, we observed (Forcade et al, Blood 2016) in the blood, a T cell subset called TFH, with B cell help capacity, similar to germinal center reaction. During cGVHD, blood TFH were highly activated, skewed toward a Th1/Th17 profile, and presented enhanced capacity to provide " help " to B cells, promoting auto-/allo-antibody production in the context of cGVHD. This was associated with increased level of CXCL13 in such patients, suggesting homing of this subset to lymphoid tissues.

Liarski et al (Sci Trans Med 2014) showed that TFH were observed in inflamed tissue sample from patients with lupus, and demonstrated close interaction with B cells, mimicking germinal center structures, such as tertiary lymphoid organs.

Preliminary data, on cGVHD tissue target, showed a CD4+ T cell infiltrate, of which some expressed CXCR5, ICOS, PD1 in single staining.

Hypothesis : cGVHD target tissue contains tertiary lymphoid structures.

Inclusion criteria

• Patient > 18 yo ;
• Having undergone an allogeneic stem cell tranplant ;
• 2 groups of patients will be eligible
• showing evidence of primary cGVHD or occuring after Donor Lymphocyte Infusion

• in the case of first occurrence of cGVHD, in the absence of any new systemic therapy ;
• in the case of recurrent cGVHD, steroid dose has to be below 15mg/day of Prednisone ;
• Having read, understood and signed an informed consent of the study;
• With social security affiliation;

Exclusion criteria

• Patient below 18 yo or unable to give consent ;
• Systemic therapy using steroids over 15mg/d of Prednisone ; and/or the use of other systemic agent introduced in the last month ;
• Haemorrhagic risk of biopsy anticipated ;
• Absence of patient agreement for the study