A survey of cancer testis antigen (CTA) expression across T-cell lymphoma subtypes.

Abstract

e15246 Background: T-cell lymphomas (TCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHL) that originate from T- and NK-cells and portends a poor prognosis. One promising therapeutic strategy involves generation of tumor associated antigen directed T-cells (TAA-T) against specific CTA. RNAseq have established that combinations of histone deacetylase inhibitors and hypomethylating agents uniquely induce genes characterized as cancer testes antigens (CTA), which may increase immunogenicity. There is a lack of data on the baseline expression of CTA across the TCL, limiting application of TAA-T. We sought to establish the baseline expression of CTA in PTCL using immunohistochemistry to better understand treatment effects. Methods: A tissue microarray was created using formalin-fixed paraffin embedded tissue from 40 patients with diverse T-cell neoplasms. Expression of WT1, SCP1, survivin, PLAC1, SSX2, and PRAME was evaluated by immunohistochemistry. The percentage of positive tumor cells (divided into quartiles), staining intensity (weak, moderate, strong), and subcellular localization (nuclear, cytoplasmic) was assessed. Results: Forty patients with T-cell lymphomas were included in the analysis. The median age of diagnosis and median number of treatments was 60.2 years and 2 (0-9), respectively. Thirty-nine (98%) patients expressed at least one CTA. A high frequency of survivin, which is associated with cell proliferation and is expressed on normal lymphoid tissue, was expressed in 98% of TCL, 5% expressed WT1, and 12.5% expressed SCP1, and expression of other CTA was not observed. Of five patients with anaplastic large cell lymphoma, 3 samples were positive for SCP1 and one was also positive for WT1. One of 9 angioimmunoblastic T-cell lymphoma samples was positive for SCP1. Of 4 T-lymphoblastic lymphoma patients, 1 was positive for WT1, and of 3 transformed mycosis fungoides specimens, 1 demonstrated SCP1 expression. In this sample set, we did not find a correlation with expression and response to chemotherapy. There were no patients with CTA expression who were treated with epigenetic treatments. Conclusions: We described low expression of CTA on T-cell lymphomas, which is consistent with the literature on expression by RT-PCR. By establishing this baseline expression of CTA, we have the foundation on which to measure changes in CTA expression pre- and post-treatment by immunohistochemistry.