Session: 622. Lymphoma Biology—Non-Genetic Studies: Poster III
Hematology Disease Topics & Pathways:
Diseases, Biological Processes, Technology and Procedures, Lymphoid Malignancies, imaging, immune mechanism, microenvironment
To date analysis of HCL immunology has been complicated by the rarity of patient samples. We were the first in the world to apply NanoString GeoMX™ digital spatial profiling (DSP) to the analysis of the expression of proteins in BM trephine samples, opening up archival samples (with accompanying long term patient follow up) in pathology departments to translational research.
In this study, we assessed HCL BM immunology pre and post CDA treatment to provide an in depth analysis of HCL immunobiology and identify pre and post treatment response biomarkers. Matched diagnostic and post CDA BM trephines from 9 HCL patients (50.2 ± 11.2 years) and 10 age matched controls (50.6 ± 13.4 years) were analyzed using DSP for the expression of 57 proteins using an immunology focused panel in immune rich regions. 6 x 300mm regions identified by dual CD3/CD45 immunofluorescent staining were analyzed per BM trephine. As the cellularity of the BM varied across samples, the results were normalized to the nuclei count for each region analysed.
The expression of the immune checkpoints CTLA-4, STING and VISTA was significantly downregulated at HCL diagnosis compared with control BM and did not recover post CDA suggesting ongoing immune dysregulation regardless of response to treatment. BCL-2 was significantly upregulated at diagnosis and returned to control levels post treatment.
To identify prognostic biomarkers, patients were classified according to their subsequent clinical course into durable vs non-durable responders. Durable responders exhibited long term responses to their initial CDA treatment (9.5 ± 4.1 years) while non-durable responders exhibited short term responses (2.25 ± 1.3 years) and required additional treatment. Durable responders had significantly increased expression of B7-H3 and decreased CD34 and FoxP3 at diagnosis and post CDA treatment exhibited significantly increased CD8, GZMB and CD68 expression suggestive of an increased environment of antigen presentation and significantly decreased CD20 expression suggestive of a deeper depletion of CD20-expressing tumor cells.
This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation of the BM that does not recover with therapy and identify biomarkers of response to standard of care CDA. Prospective application of these biomarkers will allow early identification and increased monitoring/treatment in patients at increased relapse risk post CDA treatment.
Disclosures: No relevant conflicts of interest to declare.
See more of: Oral and Poster Abstracts