Submitted by Pauline Gravelle (IUCT-ONCOPOLE, France) on Aug 03 2017
Platform: microarray – [HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [probe set (exon) version]
Pubmed: None listed
Summary We produced and analyzed the transcriptomic profiles of agressive plasmablastic lymphomas to describe their "immune escape" profile, depending on their viral status (HIV, EBV, ...). We used microarrays to compare the global gene expression profile between EBV+ and EBV- PL subtypes. This analysis unveiled the interest of treating EBV+ PL patients by immune checkpoint blockade strategies.
Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma occurring frequently in HIV-positive individuals and most often associated with Epstein Barr Virus infection. Despite recent therapeutic progress, PL still is an aggressive lymphoma with adverse prognosis. The aim of this study was to investigate whether the emerging strategies of immune checkpoint blockade could be efficient for PL patients. Here, we produced and analyzed the transcriptomic profiles of such tumors to address this question. Unsupervised hierarchical analysis of PL samples showed that PL segregated according to their EBV-status. Moreover, we report that EBV+ PL displayed a significant association with abundant leucocyte infiltrate and selective T-cell activation signatures, together with high level of inhibitory receptors and immune checkpoint markers. We propose that EBV infection induced an anti-viral cytotoxic immunity which progressively exhausted and promoted the tolerogenic tumor microenvironment of PL. Hence, most EBV+ PL patients presenting an early stage of cancer immune-editing process appear eligible for ICB immunotherapies.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM2730278 | Patient_10P6274_EBV- | plasmablastic lymphoma cell ![]() |
EBV- | Uninfected | Data failed QCpm_mean is 63.940301 (low signal, below threshold of 60)all_probeset_mad_residual_mean is 1.004244 (poor normalization, above threshold of 0.80) |
|
GSM2730279 | Patient_14P5581_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QCall_probeset_mad_residual_mean is 0.812318 (poor normalization, above threshold of 0.80) |
GSM2730280 | Patient_14P11149_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QCall_probeset_mad_residual_mean is 0.943093 (poor normalization, above threshold of 0.80) |
GSM2730281 | Patient_12P12002_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QCall_probeset_mad_residual_mean is 0.911122 (poor normalization, above threshold of 0.80) |
GSM2730282 | Patient_P14.290_EBV- | plasmablastic lymphoma cell ![]() |
EBV- | Uninfected | Data failed QC At least 40% of samples in study failed QC |
|
GSM2730283 | Patient_14P11667_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QCall_probeset_mad_residual_mean is 0.859295 (poor normalization, above threshold of 0.80) |
GSM2730284 | Patient_14P11148_EBV- | plasmablastic lymphoma cell ![]() |
EBV- | Uninfected | Data failed QCall_probeset_mad_residual_mean is 0.853151 (poor normalization, above threshold of 0.80) |
|
GSM2730285 | Patient_14T8922_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QCall_probeset_mad_residual_mean is 0.960167 (poor normalization, above threshold of 0.80) |
GSM2730286 | Patient_14T17450_EBV+ | plasmablastic lymphoma cell ![]() |
persistent | EBV+ | Human gammaherpesvirus 4 | Data failed QC At least 40% of samples in study failed QC |