Persistent donor derived Vδ4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI

Abstract

The outcome for T-cell acute lymphoblastic leukemia (T-ALL) in relapse after hematopoietic stem cell transplantation (HSCT) is quite poor, while, both donor lymphocytes infusion (DLI) and adoptively infusion of γδ T cells in leukemia patients after HSCT have demonstrated good results in prolonging survival time of patients. Here, we reported a T-ALL case who experienced three relapses and received HSCT and DLI with an overall survival (OS) time lasting for more than seven years. Based on our previous identification of a leukemic and reactive clone in this patient, continual γδ T cell repertoire monitoring affirmed that the same Vδ5 leukemic clone existed in most samples from the patient, particularly including a sample taken at the time of the third T-ALL relapse, while it could not be detected in the donor sample. In addition, an identical Vδ4 monoclonal T cell that proliferated in the recipient for several years was confirmed to come from the donor graft, and its expression level significantly increased in third leukemia recurrence. These results indicate that clonally expanded Vδ4 T cells may represent a reconstituted γδ T cell repertoire after HSCT, which also hints to a relatively better outcome for this case. Based on this case study, we recommend DLI should be as a treatment strategy for patients who achieve CR or relapse from HSCT. Moreover, dynamically monitoring the TCR repertoire in patients who receive HSCT will benefit in supervising of malignant clone evolution and residue, identifying T cell clones mediate anti-infection, GvHD or GvL.

Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia

“…We found that different oligoclonal TRDV subfamily T cells might have unique functions. We found that the clonal expansion patterns of TRDV4 and TRDV8 T cells might be independent protective factors for CR, which is consistent with our previous findings in which we found that clonally expanded TRDV4 T cells might be related to better outcome for a T-ALL patient [19]. We suggested that such expanded TRDV4 and TRDV8 T cell clones might be reactive T cell clones directed against leukemia that serve as biomarkers for the therapeutic efficacy of AML patients.…”

“…PCR product analysis produced a single dominant peak or double peaks, which demonstrate a skewed spectratype profile termed “oligoclonality” or “biclonality”, respectively. “Oligoclonality trending” is a classification with a profile between that of polyclonality and oligoclonality [19]. Clonal expansion was detected for all eight TRDV subfamilies in the γδ T cells.…”

“…In contrast, there may be clonal absence because T cell proliferation is suppressed by different factors in leukemia. For example, TRDV2 T cells are reduced and dysfunctional in some MDS patients [15, 19, 29]. To further investigate the role of oligoclonal TRDV T cells in AML patients, we first analyzed the correlation between clonally expanded TRDV T cells and clinical outcome.…”

“…Recently, it has been reported that the phenotype and distribution of γδ T cells in human breast cancer might serve as a prognostic factor predicting clinical outcome [18]. Our previous study reported that clonally expanded TRDV4 T cells might lead to relatively better outcome for patients diagnosed with T – cell acute lymphoblastic leukemia (T-ALL) after HSCT [19]. However, little is known about the correlation between γδ T cells and AML outcome.…”

Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target

“…Although hematopoietic stem cell transplantation (HSCT) provides cures in some cases, the 1-year OS following allogeneic (allo) HSCT has reached approximately 30% ( 4 – 6 ), with the majority of mortality being attributed to disease progression. Despite the poor outcomes with allo-HSCT, ALL has been shown to be responsive to immunotherapy, including donor lymphocyte infusion and adoptive T cell therapy ( 3 , 7 – 10 ). In fact, ALL is the prototype malignancy for the use of chimeric antigen receptor T cells, highlighting the potential of immunotherapy to eliminate ALL and improve patient outcomes ( 7 – 9 , 11 ).…”