T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

Wu, Hao; Sun, Hui-Cong; Ouyang, Guifang

doi:10.12998/wjcc.v10.i32.11804

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…Furthermore, galectin-9 knockout mice are more resistant to AML morbidity/mortality while double blockade of PD-1/PD-L1 and TIM-3/galectin-9 as associated with reduced leukemic burden ( 111 ). TIM-3 expression has also been found to correlate to poor prognosis in other hematologic malignancies such as DLBCL, ALL, MDS, Chronic Myelogenous Leukemia (CML), and Chronic Myelomonocytic Leukemia (CMML) ( 112 – 115 ). Thus blockade of TIM-3/galectin-9 is a potentially effective target for further treatment in several hematologic malignancies.…”

Section: Other Targetable Checkpoint Moleculesmentioning

confidence: 99%

Checkpoint inhibition in hematologic malignancies

Tsumura,

Levis,

Tuscano

2023

Front. Oncol.

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Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.

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Section: Other Targetable Checkpoint Moleculesmentioning

confidence: 99%

Checkpoint inhibition in hematologic malignancies

Tsumura,

Levis,

Tuscano

2023

Front. Oncol.

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“…In many tumors such as melanoma [ 17 ] and gastric cancer [ 18 ], the increase of TIM3 is associated with poor prognosis and CD8 + TILs exhaustion. Nevertheless, there are contradictory conclusions about the effect of TIM3 expression on the prognosis of DLBCL patients [ 3 , 6 , 13 , 19 , 20 ]. Previous studies demonstrated that the increase of TIM3 may be related to CD8 + TILs exhaustion and immune deficiency in DLBCL [ 13 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway

Zhu,

Yang,

Chen

et al. 2024

J Transl Med

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Background Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, the mechanism of TIM3-mediated CD8+TILs exhaustion in DLBCL remains poorly understood. Therefore, we aimed to clarify the potential pathway involved in TIM3-mediated CD8+TILs exhaustion and its significance in DLBCL. Methods The expression of TIM3 and its correlation with CD8+TILs exhaustion, the key ligand of TIM3, and the potential pathway of TIM3-mediated CD8+TILs exhaustion in DLBCL were analyzed using single-cell RNA sequencing and validated by RNA sequencing. The biological significance of TIM3-related pathway in DLBCL was investigated based on RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction data. Finally, the possible regulatory mechanism of TIM3-related pathway in DLBCL was explored using single-cell RNA sequencing and RNA sequencing. Results Our results demonstrated that CD8+TILs, especially the terminally exhausted state, were the major clusters that expressed TIM3 in DLBCL. Galectin-9, mainly expressed in M2 macrophages, is the key ligand of TIM3 and can induce the exhaustion of CD8+TILs through TIM3/Galectin-9 pathway. Meanwhile, high TIM3/Galectin-9 enrichment is related to immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, and poor response to CHOP-based chemotherapy, and can predict the clinical efficacy of immune checkpoint blockade therapy in DLBCL. Furthermore, the TIM3/Galectin-9 enrichment in DLBCL may be regulated by the IFN-γ signaling pathway. Conclusions Our study highlights that TIM3/Galectin-9 pathway plays a crucial role in CD8+TILs exhaustion and the immune escape of DLBCL, which facilitates further functional studies and could provide a theoretical basis for the development of novel immunotherapy in DLBCL.

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“…Prognostic biomarkers provide basic information for predicting treatment outcomes and survival and therefore play a vital role in achieving reliable and accurate treatment predictions. Currently, CD97B mutation, CD30 expression and T-cell immunoglobulin mucin molecule-3 (Tim-3) expression have been confirmed as prognostic biomarkers of DLBCL ( 3 ), but these indicators are not widely used clinically due to technical limitations or difficulty in obtaining them ( 4 , 5 ). Hence, there is a need for prognostic clinical markers that are cost-effective, simple, and readily available.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of baseline C-reactive protein in diffuse large B-cell lymphoma: a systematic review and meta-analysis

Huang,

Wang,

Huang

et al. 2023

Transl Cancer Res

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Background C-reactive protein (CRP) is an inflammatory marker of great significance for progression and prognosis of diffuse large B-cell lymphoma (DLBCL). However, previous studies reported the inconsistent findings of the relationship between CRP levels and survival in DLBCL patients. This meta-analysis was performed to investigate the predictive value of baseline CRP in the prognosis of DLBCL. Methods Relevant studies on baseline CRP and prognosis of DLBCL were searched from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and other databases. The search time was from establishment of the database to December 2022. The studies that reported the baseline CRP level, DLBCL confirmed by pathology, data on the relationship between CRP and overall survival (OS) or progression-free survival (PFS), and published in English or Chinese were included in this meta-analysis. No evidence showed the risk of bias of the included studies. Random-effects meta-analysis were conducted to calculate hazard ratio (HR). Stata15.0 software was used for the meta-analysis. Results A total of 11 studies with 2,314 patients were included. All included studies were of high quality. The result of prognosis in patients with CRP and DLBCL was HR =2.48 [95% confidence interval (CI): 1.52 to 4.07]. The subgroup analysis showed that the risk of death was higher in both groups (HR =2.58, 95% CI: 2.10 to 3.18, random effects model I 2 =39.7%). There was a significant difference between group 1 and group 2 (P=0.000). Conclusions Current evidence suggests that baseline CRP is a potential predictor of DLBCL patients and has potential prognostic value in clinical practice, improving the survival rate and quality of life of DLBCL patients. Additionally, OS appears to be strongly influenced by potential country specific differences, which may be related to racial differences and specific lifestyles.

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T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

Cited by 5 publications

References 21 publications

Checkpoint inhibition in hematologic malignancies

Checkpoint inhibition in hematologic malignancies

Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway

Prognostic value of baseline C-reactive protein in diffuse large B-cell lymphoma: a systematic review and meta-analysis

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