332O - Co-expression of PD-L1 and p-AKT is associated with poor prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular AK...

Date 19 December 2016
Event ESMO Asia 2016 Congress
Session Haematological malignancies
Topics Lymphomas
Translational Research
Presenter Huilai Zhang
Citation Annals of Oncology (2016) 27 (suppl_9): ix104-ix111. 10.1093/annonc/mdw586
Authors H. Zhang1, X. Wang1, L. Dong1, H. Lv1, W. Li1, Z. Song1, L. Li1, S. Zhou1, L. Qiu1, Z. Qian1, X. Liu1, L. Feng1, B. Meng2, K. Fu3, X. Wang4, Q. Pan-Hammarström5, P. Wang6
  • 1Department Of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, 300060 - Tianjin/CN
  • 2Department Of Pathology, Tianjin Medical University Cancer Institute and Hospital, 300060 - Tianjin/CN
  • 3Department Of Pathology And Microbiology And Internal Medicine, University of Nebraska Medical Center, 432346 - Omaha/US
  • 4Department Of Cellular Biology, Tianjin Medical University, 300060 - Tianjin/CN
  • 5Department Of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, 345221 - Stockholm/SE
  • 6Department Of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, 300060 - Tianjin/CN

Abstract

Background

Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) engagement usually leads to diminished antitumor T-cell responses, which mediates the immune escape of tumor cells. However, little is known whether PD-1/PD-L1 could directly activates intracellular oncogenic signaling pathways in tumor cells. The purpose of this study is to investigate whether intracellular AKT/mTOR signaling could be directly activated by PD-1/PD-L1 during the malignant progression in diffuse large B-cell lymphoma (DLBCL).

Methods

The immunohistochemistry (IHC) was used to detect expression of PD-L1 and p-AKT. Total PD-L1 proteins of DLBCL cells was determined by western blot. The membrane PD-L1 (mPD-L1) proteins of DLBCL cells was determined by flow cytometry. The survival analysis was performed using Kaplan-Meier method.

Results

Detection of the expression of PD-L1 and p-AKT by immunohistochemistry (IHC) showed that both proteins were overexpressed in 54% and 48% DLBCL cases, respectively. Spearman test showed that PD-L1 expression was correlated with p-AKT expression (R = 0.244, χ2=5.962; P = 0.017) and the expression of PD-L1 and p-AKT were also correlated with clinic-pathological characteristics. In addition, survival analysis showed that DLBCL patients who co-expressed PD-L1 and p-AKT had significantly poorer outcome than patients with single positive or both negative expression (P 

Conclusions

Our results suggested that the combination of PD-1/PD-L1 antibodies and AKT/mTOR inhibitor might be a promising and novel therapeutic approach for DLBCL in the future.

Clinical trial indentification

ChiCTR-ONC-12002385

Legal entity responsible for the study

N/A

Funding

Natural Science Foundation of China (81402945)

Disclosure

All authors have declared no conflicts of interest.