Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma

Zhang, Li; Du, Huarui; Xiao, Taiwu; Liu, Ji-zhu; Liu, Guozhen; Wang, Jingxia; Li, Guangyao; Wang, Lexin

doi:10.1016/j.biopha.2015.08.037

Cited by 36 publications

(33 citation statements)

References 24 publications

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“…Compared to the unpretreated, fewer pretreated patients had TIM-3 C TILs in their stroma, which is in line with findings from Zhang et al in diffuse large B-cell lymphoma. 24 A stromal immune cell score of 3 was more often found for pretreated samples, suggesting that chemotherapy causes an increase in immune infiltration. This is in concordance with findings in other tumor types, showing that cisplatin promotes recruitment and proliferation of effector immune cells.…”

Section: Discussionmentioning

confidence: 98%

“…This is in line with the finding of Zhang et al that large B-cell lymphoma patients with low PD-1 expression on T cells are more likely to respond to chemotherapy. 24 Results derived from an immunodeficient mesothelioma mouse model suggest that the effect of pemetrexed is mediated through activation of CD8 C T cells, rather than direct killing of tumor cells. 25 Since more PD-1 expression can point at exhausted CD8 C T cells, this might decrease the antitumor efficiency of pemetrexed.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

et al. 2016

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Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value.To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy). We stained for PD-1, PD-L1, TIM-3, LAG-3, CD4, CD8, CD45RO, granzyme B, FoxP3 and CD68. Furthermore, we analyzed the relationship between the immunological parameters and survival, as well as response to chemotherapy. We found that TIM-3, PD-1 and PD-L1 were expressed on both immune and tumor cells. Strikingly, PD-1 and PD-L1 expression on tumor cells was only seen in unpretreated samples. No LAG-3 expression was observed. CD45RO expression in the stroma was an independent negative predictive factor for response on chemotherapy, while CD4 and TIM-3 expression in lymphoid aggregates were independent prognostic factors for better outcome. Our data propose TIM-3 as a promising new target in mesothelioma. Chemotherapy influences the expression of immune checkpoints and therefore further research on the best combination treatment schedule is required.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

et al. 2016

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“…Furthermore, a number of molecular signatures have also shown prognostic roles, such as PD-1 and TIM-3 expression concentrations [25], E2F1 expression [26], nuclear and cytoplasmic NF-κB expression [27] and LincRNA-p21expression [28]. However, molecular marker is associated with high costs and time-consuming procedures and is not routinely available in most laboratories.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment C-reactive protein was an independent prognostic factor for patients with diffuse large B-cell lymphoma treated with RCHOP

Wang

Zhou

Wang

et al. 2016

Clinica Chimica Acta

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“…Despite abundant data characterizing CD4 + T-cells and their subsets in B-cell Non-Hodgkin lymphoma (B-NHL) (1), and in particularly chronic lymphocytic leukemia (CLL) (2-6), their role in disease development and progression is poorly understood. Besides well-known T helper (Th) cell subsets (5), interleukin (IL-)10 producing, FOXP3 - conventional CD4 + T-cells, named type 1 regulatory (T R 1) cells, are gaining attention in mouse models as well as patients harboring chronic inflammatory conditions such as inflammatory bowel disease (7-10).…”

Section: Introductionmentioning

confidence: 99%

“…In B-NHL, an increased expression of PD-1 in blood-derived CD4 + T-cells was reported for diffuse large B-cell lymphoma (DLBCL) (1, 11) as well as for CLL (4, 12, 13). In a preclinical study, a blocking antibody against the PD-1 ligand 1 (PD-L1) showed high activity in controlling CLL progression in the Eµ-TCL1 mouse model (14).…”

Section: Introductionmentioning

confidence: 99%

EOMES and IL-10 regulate anti-tumor activity of PD-1⁺CD4⁺T-cells in B-cell Non-Hodgkin lymphoma

Roessner

Lupar

et al. 2020

Preprint

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41The transcription factor Eomesodermin (EOMES) promotes IL-10 production of CD4 + T-cells, which has 42 been linked to immunosuppressive and cytotoxic activities. We detected EOMES-expressing CD4 + T-43 cells in lymph node samples of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell 44 lymphoma. This was in line with an observed expansion of EOMES-positive CD4 + T-cells in leukemic Eµ-45 TCL1 mice, a well-established model of CLL, and upon adoptive transfer of TCL1 leukemia in mice. 46Transcriptome and flow cytometry analyses revealed that EOMES does not only drive the transcription 47 of IL-10, but rather controls a unique differentiation program in CD4 + T-cells. Moreover, EOMES was 48 necessary for the accumulation of a specific CD4 + T-cell subset that expresses IFNγ and IL-10, as well 49 as inhibitory receptors, like PD-1 and LAG3. T-cell transfer studies in leukopenic Rag2 -/mice showed 50 that EOMES-deficient CD4 + T-cells were inferior in controlling TCL1 leukemia development compared 51 to wildtype T-cells, even though expansion of Eomes -/-CD4 + T-cells was observed. We further showed 52 that control of TCL1 leukemia was driven by IL-10 receptor-mediated signals, as Il10rb-deficient CD4 + 53 T-cells showed impaired anti-leukemia activity. Altogether, our data suggest that IL-10 producing PD-54

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Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma

Cited by 36 publications

References 24 publications

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Pretreatment C-reactive protein was an independent prognostic factor for patients with diffuse large B-cell lymphoma treated with RCHOP

EOMES and IL-10 regulate anti-tumor activity of PD-1⁺CD4⁺T-cells in B-cell Non-Hodgkin lymphoma

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Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma

Cited by 36 publications

References 24 publications

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma

Pretreatment C-reactive protein was an independent prognostic factor for patients with diffuse large B-cell lymphoma treated with RCHOP

EOMES and IL-10 regulate anti-tumor activity of PD-1+CD4+T-cells in B-cell Non-Hodgkin lymphoma

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EOMES and IL-10 regulate anti-tumor activity of PD-1⁺CD4⁺T-cells in B-cell Non-Hodgkin lymphoma