Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia

Shiyi Pan; Qinghua Cai; Yiqiong Wei; Haifeng Tang; Yuping Zhang; Wei Zhou; Tingfen Deng; Wenjian Mo; Shunqing Wang; Caixia Wang; Cunte Chen

doi:10.1016/j.imbio.2024.152804

Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia

Immunobiology. 2024 Apr 11;229(3):152804. doi: 10.1016/j.imbio.2024.152804. Online ahead of print.

Authors

Shiyi Pan¹, Qinghua Cai¹, Yiqiong Wei², Haifeng Tang³, Yuping Zhang¹, Wei Zhou¹, Tingfen Deng¹, Wenjian Mo¹, Shunqing Wang⁴, Caixia Wang⁵, Cunte Chen⁶

Affiliations

¹ Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China.
² Department of Neurology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China.
³ Department of Surgery, The Third School of Clinical Medicine, Southern Medical University, Guangzhou 516006, China.
⁴ Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China. Electronic address: shqwang_cn@163.com.
⁵ Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China. Electronic address: wangcx225@163.com.
⁶ Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China. Electronic address: cuntechen@163.com.

PMID: 38615511
DOI: 10.1016/j.imbio.2024.152804

Abstract

Background: Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known.

Methods: The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation.

Results: In both GZFPH and TCGA cohorts, high expression of ICOS was significantly associated with poor overall survival (OS) in patients with AML (P < 0.05). Importantly, co-expression of ICOS and PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 predicted poor OS in AML; among them, ICOS/PD-1 was the optimal combination of immune checkpoints (ICs). The co-expression of ICOS and PD-1 was correlated with poor OS in non-acute promyelocytic leukemia (non-APL) patients following chemotherapy. Additionally, ICOS/PD-1 was an independent OS-predicting factor (P < 0.05). Notably, a nomogram model was constructed by combining ICOS/PD-1, age, European Leukemia Net (ELN) risk stratification, and therapy to visually and personalized predict the 1-, 3-, and 5-year OS of patients with non-APL.

Conclusion: Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.

Keywords: Acute myeloid leukemia; Biomarker; Immune checkpoint; Prognosis.