Optimal combination of immune checkpoint and senescence molecule predicts adverse outcomes in patients with acute myeloid leukemia

Wang, Peipei; Zhang, Yuling; Cai, Qinghua; Long, Qingqin; Pan, Shiyi; Wei, Zhou; Deng, Tingfen; Mo, Wenjian; Wang, Shunqing; Zhang, Yuping; Wang, Caixia; Chen, Cunte

doi:10.1080/07853890.2023.2201507

Cited by 8 publications

(3 citation statements)

References 50 publications

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“…Noteworthily, however, a significantly higher survival of AML patients was demonstrated in groups with a lower percentage of Th lymphocytes expressing B7-H3. These clinical data substantially complement previous results of available dataset analysis or clinical observations that highlighted a poor prognosis for survival of AML subjects showing a high expression of B7-H3 [45,46]. Although statistically significant, results of our survival analysis must be used with caution when assessing other patients' risk due to the fact that borderline p levels were reached.…”

Section: Discussionsupporting

confidence: 82%

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Bolkun,

Tynecka,

Walewska

et al. 2023

Cancers

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The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients’ survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

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Section: Discussionsupporting

confidence: 82%

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Bolkun,

Tynecka,

Walewska

et al. 2023

Cancers

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“…CD276 , also known as B7-H3 , belongs to the B7 family of immune checkpoint molecules. High expression of B7-H3 was found to be associated with poor overall survival in AML patients 37 . Our study supports these observations by showing a positive association between CD276 expression and the risk score.…”

Section: Discussionmentioning

confidence: 95%

Identification and validation of a prognostic risk-scoring model based on the level of TIM-3 expression in acute myeloid leukemia

Huang,

Zheng,

Wang

et al. 2023

Sci Rep

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Acute myeloid leukemia (AML) is characterized by an unfavorable prognosis due to the presence of self-renewing leukemic stem cells (LSCs). The presence of T-cell immunoglobulin mucin-3 (TIM-3) on the surface of LSCs has been observed in various types of human AML, exerting an impact on the prognostic outcome. Exploring the hub genes associated with varying levels of TIM-3 expression offers a valuable approach to enhance our understanding of the underlying mechanisms involving TIM-3 and to identify potential prognostic indicators in AML. Nevertheless, to date, no research studies have reported a prognostic model that relies on the level of TIM-3 expression. In our study, we screen the hub-genes based on different expression level of TIM-3 through WGCNA. The prognostic risk-scoring model was constructed based on hub-genes. The results show the risk prognostic model has extraordinary ability to predict prognosis in both the training and validation sets. The high-risk group present poor prognosis with mutation of NPM1, TP53 (Multiple Hit) and FLT3(multiple hit), while IDH2 (Missense Mutation), MUC16 (Multiple Hit/Missense Mutation) occur mutation in low-risk group presenting favorite prognosis than high-risk group. Leukocyte cell–cell adhesion, regulation of T cell activation and I-κB kinase/NF-κB signaling enriched in high-risk group, involving in HSCs or LSCs anchoring to BM, which implicated in LSCs survival and chemotherapy resistance. B7-H3 (CD276) and CD276 would be the potential immune targets in high-risk group. The risk score model may help in distinguishing immune and molecular characteristics, predicting patient outcomes.

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“…T cell senescence is also related to tumor immune evasion and poor prognosis. 22,23 As T cells differentiate, replicate, and age, their expression of costimulatory molecules CD27 and CD28 decreases and that of CD57 increases. 24 We further compared the expression levels of these molecules in the 2 subpopulations.…”

Section: Bm Cd8 + Trm-like Subset Highly Expresses Co-inhibitory Mole...mentioning

confidence: 99%

High percentage of bone marrow CD8+ tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia

Cai,

Lai,

Yao

et al. 2024

Blood Science

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Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, the proportion and prognostic value of TRM cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML (ND-AML). We found that the BM CD8+ effector memory (TEM) cells highly expressed CD69 (CD8+ TRM-like T cells), and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals (HI). The high percentage of CD8+ TRM-like subset was associated with poor overall survival in our ND-AML cohort. The Kaplan–Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8+ TRM-like T cell characteristic genes (CD8A, CD69, and TOX), especially the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8+ TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8+ T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules. In conclusion, we found that the accumulation of BM CD8+ TRM-like cells could be an immune-related survival prediction marker for patients with AML.

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Optimal combination of immune checkpoint and senescence molecule predicts adverse outcomes in patients with acute myeloid leukemia

Cited by 8 publications

References 50 publications

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Identification and validation of a prognostic risk-scoring model based on the level of TIM-3 expression in acute myeloid leukemia

High percentage of bone marrow CD8+ tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia

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