256O - Associations of OX40 and tumour microenvironment with outcomes in diffuse large B-cell lymphoma

Background

OX40, a novel costimulatory molecule expressed on activated T cells, plays an important role in enhancing the anti-tumor immune response. However, little is known about how OX40 functions in microenvironment in diffuse large B-cell lymphoma (DLBCL). The aims of this study were to determine the OX40 expression in DLBCL microenvironment and the relationship with the prognosis of patients.

Methods

The OX40 mRNA expression between DLBCL tissues and normal tissues, and its associated with survival were analyzed through Oncomine. The CD4, CD8, Pax-5, OX40 and Foxp3 multiplexed immunofluorescence staining, and quantitative analyses of OX40+ tumor-infiltrating T-lymphocytes were performed in DLBCL biopsy samples.

Results

We found that the OX40 mRNA expression was significantly upregulated in DLBCL patients through Oncomine (p<0.001) and high OX40 mRNA expression was significantly correlated with the favorable prognosis (p=0.018). The total OX40+ cells expression level in patients was significantly associated with Ann Arbor stage (p=0.039) and IPI score (p=0.047). The expression of OX40, compared with that in stable disease (SD)/progressive disease (PD) patients, was significantly increased in complete response (CR) or partial response (PR) patients (p=0.002; p=0.002, respectively). A higher total expression of OX40 and a greater number of CD8+/OX40+ T-cells were significantly correlated with longer overall survival (OS) (p=0.008; p=0.004, respectively). The expression of CD8+/OX40+ T-cells maintained prognostic value for OS in multivariate analysis (p=0.030; p=0.024, respectively).

Conclusions

Here, for the first time, we describe the expression characteristics of OX40 and tumor microenvironment in DLBCL through multiple immunofluorescence staining and quantitative pathological analysis techniques, and the association between OX40 expression and outcomes, providing a theoretical foundation for the potential clinical transformational application value of OX40 agonists for DLBCL therapy.

Clinical trial identification

Editorial acknowledgement

All authors thank the National Human Genetic Resources Sharing Service Platform/Cancer Biobank of Tianjin Medical University Cancer Institute and Hospital grant 2005DKA21300 for the support of patient tissues.

Legal entity responsible for the study

The Research Ethics Committee of the Tianjin Medical University Cancer Institute and Hospital (TMUCIH) approved the study, which was conducted in accordance with the Declaration of Helsinki.

Funding

This work was supported by Natural Science Foundation of Tianjin grants 19JCYBJC26500 and 18JCZDJC45100), National Natural Science Foundation of China grants 81770213 and 81670184, National Key New Drug Creation Special Programs grants 2017ZX09304-021 and 2018ZX09201015, Clinical Oncology Research Fund of CSCO grant Y-XD2019-162.

Disclosure

All authors have declared no conflicts of interest.