CD70 Expression in Mature T-Cell Lymphomas

Introduction

Mature T-cell lymphomas (TCLs) represent about 15% of the non-Hodgkin lymphomas in U.S. and are a heterogeneous group of neoplasms. TCLs usually have poor outcomes and are resistant to conventional chemotherapy regimens. Therefore, there is a need for identifying biomarkers that could translate into effective novel treatments. CD70 is the TNF superfamily ligand of CD27 and it is being explored as a potential target in CAR-T therapy against TCLs and other neoplasms. Although CD70 expression has been documented in TCL cell lines, thus providing a potential rationale for its use as a therapeutic target, the expression of CD70 among the most frequent TCL subtypes in patient samples has not been previously evaluated.

Methods

Patients with de novo and/or relapsed mature TCLs diagnosed between 01/2010 and 06/2020 and with available tissue sections were included in the study. The assessment of CD70 expression was performed by immunohistochemistry (IHC) using a novel proprietary antibody developed by CRISPR Therapeutics. CD70 expression was scored using % of expression, intensity (negative, +1, +2, and +3) and H-score {H-score = [(%positive cells intensity 1+) x 1] + [(%positive cells intensity 2+) x 2] + [(%positive cells intensity 3+) x 3]} in neoplastic cells (Figure 1). Clinicopathologic characteristics were collected retrospectively and included age, sex, staging, biopsy site, WHO pathologic classification, immunophenotype, presence of other malignancies, treatment status, disease progression/relapsed, and follow-up. These characteristics were compared with CD70 expression using ANOVA or non-parametric analysis. Overall-survival (OS) was estimated using Kaplan-Meier method and compared using log-rank. A p< 0.05 was considered statistically significant.

Results

One hundred thirty-six patient samples representing the major subtypes of the 4 categories of mature TCLs were included [nodal TCLs (n=64; including PTCL Th1, and Th2 subtypes and angioimmunoblastic T cell lymphoma - AITL), extranodal (n=35; including primary intestinal lymphomas), cutaneous (n=24; including mycosis fungoides (MF) with large cell transformation), and leukemic (n=13; including adult T cell leukemia/lymphoma)]. Most patients were male (58.8%), in the 6 ^th or 7 ^th decade (47.1%), with advanced stage IV (55.7%), no previous malignancies (69.9%) and previously treated (57.2%); 59 of which (88%) received two or more lines of treatment. The median expression of CD70 was 40% (ranged from 0 to 100%) and the median H-score was 110 (ranged from 0 to 300) and was significantly higher (p= 0.006) in peripheral T-cell lymphoma, NOS, primary cutaneous TCLs (non-mycosis fungoides), and AITL (180, 150, and 150, respectively) (Figure 1). The expression of CD70 was more frequent in nodal and extranodal subtypes (including skin), compared to leukemic TCLs (p= 0.005). The expression of CD70 was associated with advanced age at the diagnosis (p= 0.003), CD2 expression (p= 0.01), CD3 expression (p= 0.001), CD16 negativity (p= 0.03), and absence of ALK-1 expression (p= 0.005). After a median follow-up of 19 months (range: 1 - 300 months), 42% of the patients died of disease. The median OS was 76 months (CI95, 38.5 - 113.4 months) and it was not associated with CD70 expression.

Conclusions

CD70 was highly expressed in most mature TCLs and it was negative in most ALK-positive ALCL. Its expression was associated with nodal and extranodal subtypes, advanced age, expression of CD2, CD3, and negativity for CD16. Therefore, CD70 can be used as a potential biomarker and a target in clinical trials of patients with mature TCLs.

Figure 1

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Figure 1

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