OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy in diffuse large B-cell lymphoma

Lu, Yaxiao; Li, Yang; Yu, Jingwei; Meng, Shen; Bi, Chengfeng; Guan, Qingpei; Li, Lanfang; Qiu, Lihua; Qian, Zhengzi; Zhou, Shunhua; Gong, Wenchen; Meng, Bin; Ren, Xiubao; Armitage, Jamés O.; Zhang, Huilai; Fu, Kai; Li, Linyu

doi:10.1016/j.clim.2023.109637

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…DLBCL is the most common subtype of aggressive lymphoma with certain patients who cannot benefit from the current treatment [ 2 ], and novel therapeutic targets were needed to explore. The disorder of TME plays a vital role in the development and metastasis of DLBCL [ 5 , 6 ], among which CD8 + TILs are indispensable for tumor eradication and prognosis evaluation [ 7 , 8 ]. Recently, Zhao et al demonstrated the exhaustion status of CD8 + TILs in DLBCL and constructed a prognostic model based on the associated genes [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…TILs are crucial members of TME in DLBCL, in which CD8 + TILs are the main components that deliver anti-tumor immune response [ 7 , 8 ]. We previously analyzed the characteristics of TME in DLBCL by flow cytometry and found that CD8 + TILs may be an important cause of the heterogeneity in DLBCL [ 9 ], and the proportion of CD8 + TILs and the expression of PD-1 play a pivotal role in prognosis evaluation [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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Prognostic analysis of prostaglandin D2 synthase in diffuse large B-cell lymphoma

Wang,

Xu,

et al. 2023

Holist Integ Oncol

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Purpose We aimed to analyse the correlation between prostaglandin D2 synthase (PTGDS) and a diffuse large B-cell lymphoma (DLBCL) prognosis. Methods We retrospectively collected two hundred paraffin-embedded tissue specimens that were pathologically diagnosed as DLBCL in the Fujian Tumour Hospital between January 2014 and December 2018. An abundance of paraffin-embedded tumour tissues were obtained. Twenty patients with lymphocyte-rich, benign, tissue-reactive, hypertrophic tonsillitis were selected as controls. Wax blocks were selected for primary cases and the controls were screened by professional pathologists. The levels of prostaglandin D2 synthase (PTGDS) and the EMT-related molecules, E-cadherin and vimentin, were detected by immunohistochemistry in clinical samples. A chi-square test revealed the correlations between PTGDS expression and clinicopathological characteristics, including age, sex, primary site, clinical stage, immunotyping, and International Prognostic Index (IPI) score. The Kaplan–Meier survival analysis was performed, and the diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. Results A total of 138 cases (69%) were found to be PTGDS positive (> 30% positive cells). PTGDS staining was negative (< 30% positive cells) in 62 cases (31%). We collected the corresponding clinicopathological information and found that PTGDS expression was not significantly related to the patients’ age, tumour stage, presence of extranodal invasion, or IPI score. According to the follow-up data, patients with low PTGDS expression had poor progression-free survival (PFS) and overall survival (OS), with 2-year PFS and OS rates of 41.7% and 50%, respectively. The 2-year PFS and OS rates of PTGDS-positive patients were 89.3% and 92.9%, respectively (P < 0.0001), and the differences were significant. Conclusion We found that the expression level of PTGDS is significantly correlated with the prognosis of diffuse large B-cell lymphoma.

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TIGIT: Will it be the next star therapeutic target like PD-1 in hematological malignancies?

Liu,

2024

Critical Reviews in Oncology/Hematology

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OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy in diffuse large B-cell lymphoma

Cited by 5 publications

References 41 publications

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

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

Prognostic analysis of prostaglandin D2 synthase in diffuse large B-cell lymphoma

TIGIT: Will it be the next star therapeutic target like PD-1 in hematological malignancies?

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