Generation of human autologous cutaneous B cell lymphoma-specific cytotoxic T cells from tumor-infiltrating lymphocytes

1992 ◽  
Vol 4 (2) ◽  
pp. 125
Author(s):  
K. Maeda ◽  
M. Oishi ◽  
M. Takahashi
2007 ◽  
Vol 137 (4) ◽  
pp. 364-373 ◽  
Author(s):  
Sverker Hasselblom ◽  
Margret Sigurdadottir ◽  
Ulrika Hansson ◽  
Herman Nilsson-Ehle ◽  
Börje Ridell ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Zihang Chen ◽  
Xueqin Deng ◽  
Yunxia Ye ◽  
Wenyan Zhang ◽  
Weiping Liu ◽  
...  

The PD1/PDL1 status of tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL) reflects immune function. However, the previously reported methods for evaluating this status are complex and may not be widely used in clinical practice. In addition, these studies did not introduce healthy controls to designate the cut-off when evaluating the prognostic value of the status. In this study, we retrospectively evaluated the PD1/PDL1 status in TILs of 24 DLBCL tissue samples and normal immune cells in 61 demographically matched healthy controls (tissue samples from patients with reactive hyperplasia [RH]) by flow cytometry. We investigated the prognostic value of the PD1/PDL1 status in TILs by precisely determining the cut-off value and assessing the reliability of flow cytometry. The mean fluorescence intensity (MFI) of PD1 in TIL-T-cells (TIL-Ts; median, 110) and CD8+TIL-Ts (median, 64) was significantly higher than that of CD3+T-cells (median, 64) and CD8+ T-cells (median, 34) in RH. The cut-off values of PD1/PDL1 status for analyzing prognostic values were defined considering the PD1/PDL1 status of samples from both patients with DLBCL and healthy controls. High MFI of PD1 in TIL-Ts (MFI >108, P = 0.022), high proportion of PD1+CD4+TIL-Ts (>1.1% of CD4+TIL-Ts, P = 0.049), high proportion of PD1+CD8+TIL-Ts (>2% of CD8+TIL-Ts, P = 0.025), and high MFI of PDL1 in TIL-Ts (MFI >83, P = 0.023) were risk factors for inferior prognosis of DLBCL. Our results indicate that flow cytometry is a reliable and convenient method for evaluating the immune-checkpoint status of TILs, which probably holds major implications in clinical practice.


2019 ◽  
Vol 5 (5) ◽  
pp. eaau5240 ◽  
Author(s):  
M. Feng ◽  
J. Q. Jin ◽  
L. Xia ◽  
T. Xiao ◽  
S. Mei ◽  
...  

The Wnt/β-catenin (β-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of β-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9CT-24, that robustly inhibits the activity of β-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (Treg) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between Treg infiltration and APC mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/β-cat signaling.


2007 ◽  
Vol 48 (7) ◽  
pp. 3223 ◽  
Author(s):  
Vale´rie Touitou ◽  
Ce´cile Daussy ◽  
Bahram Bodaghi ◽  
Serge Camelo ◽  
Yvonne de Kozak ◽  
...  

2010 ◽  
Vol 29 (1) ◽  
pp. 47-53 ◽  
Author(s):  
S. Muenst ◽  
S. Hoeller ◽  
N. Willi ◽  
S. Dirnhofer ◽  
A. Tzankov

Aims: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas.Methods: Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. Results: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells.Conclusions: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.


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