Immune Signature Drives Leukemia Relapse after Transplantation
By LabMedica International staff writers Posted on 11 Apr 2019 |
Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent.
A transcriptional signature that is associated with relapse among leukemia patients who have undergone stem cell transplants has been discovered. For many patients, there is an immune pattern that occurs at relapse and could suggest a targeted therapy.
Hematologists and their associates at the IRCCS San Raffaele Scientific Institute (Milan, Italy) used samples from 40 adult patients who had undergone transplantation for acute myeloid leukemia (AML) and for whom samples had been collected at diagnosis, relapse after chemotherapy, and relapse after allo-HCT. They isolated leukemic cells from these samples and analyzed the blast cells using single nucleotide polymorphism (SNP) arrays and gene expression arrays.
The scientists identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell co-stimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple co-stimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells.
After confirming the changes in B7-H3 and CD11A levels that were indicated by the gene expression analysis, the team also noted the upregulation of PD-L1, PVRL2, and CD80 after relapse. In particular, they found that the percentage of T cells expressing PD-1 was higher among AML patients before transplantation, as compared to healthy controls, and that it levels were similarly high in patients in remission and became even higher among post-transplant relapse patients.
They also noted also noted that post-transplantation relapse patients exhibited downregulation of almost all HLA class II transcripts. When they tested T cells collected from a patient who experienced relapse after a loss of HLA class II expression, they found that this person's T cells responded to the leukemia they had at diagnosis, but not at relapse. However when exposed to IFN-γ, the leukemia cells exhibited increased HLA class II expression, allowing the T cells to once again target those cells.
The authors concluded that their results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies. The study was published on March 25, 2019, in the journal Nature Medicine.
Related Links:
IRCCS San Raffaele Scientific Institute
A transcriptional signature that is associated with relapse among leukemia patients who have undergone stem cell transplants has been discovered. For many patients, there is an immune pattern that occurs at relapse and could suggest a targeted therapy.
Hematologists and their associates at the IRCCS San Raffaele Scientific Institute (Milan, Italy) used samples from 40 adult patients who had undergone transplantation for acute myeloid leukemia (AML) and for whom samples had been collected at diagnosis, relapse after chemotherapy, and relapse after allo-HCT. They isolated leukemic cells from these samples and analyzed the blast cells using single nucleotide polymorphism (SNP) arrays and gene expression arrays.
The scientists identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell co-stimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple co-stimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells.
After confirming the changes in B7-H3 and CD11A levels that were indicated by the gene expression analysis, the team also noted the upregulation of PD-L1, PVRL2, and CD80 after relapse. In particular, they found that the percentage of T cells expressing PD-1 was higher among AML patients before transplantation, as compared to healthy controls, and that it levels were similarly high in patients in remission and became even higher among post-transplant relapse patients.
They also noted also noted that post-transplantation relapse patients exhibited downregulation of almost all HLA class II transcripts. When they tested T cells collected from a patient who experienced relapse after a loss of HLA class II expression, they found that this person's T cells responded to the leukemia they had at diagnosis, but not at relapse. However when exposed to IFN-γ, the leukemia cells exhibited increased HLA class II expression, allowing the T cells to once again target those cells.
The authors concluded that their results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies. The study was published on March 25, 2019, in the journal Nature Medicine.
Related Links:
IRCCS San Raffaele Scientific Institute
Latest Immunology News
- Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
- AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
- Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
- Testing Method Could Help More Patients Receive Right Cancer Treatment
- Groundbreaking Test Monitors Radiation Therapy Toxicity in Cancer Patients
- State-Of-The Art Techniques to Investigate Immune Response in Deadly Strep A Infections
- Novel Immunoassays Enable Early Diagnosis of Antiphospholipid Syndrome
- New Test Could Predict Immunotherapy Success for Broader Range Of Cancers
- Simple Blood Protein Tests Predict CAR T Outcomes for Lymphoma Patients
- Cell Sorter Chip Technology to Pave Way for Immune Profiling at POC
- Chip Monitors Cancer Cells in Blood Samples to Assess Treatment Effectiveness
- Automated Immunohematology Approaches Can Resolve Transplant Incompatibility
- AI Leverages Tumor Genetics to Predict Patient Response to Chemotherapy
- World’s First Portable, Non-Invasive WBC Monitoring Device to Eliminate Need for Blood Draw
- Predictive T-Cell Test Detects Immune Response to Viruses Even Before Antibodies Form
- Single Blood Draw to Detect Immune Cells Present Months before Flu Infection Can Predict Symptoms