Tumor-associated myeloid derived suppressor cells of granulocytic nature as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19040-e19040
Author(s):  
Kalyan Kusum Mukherjee ◽  
Sukanya Dhar ◽  
Mohona Chakraborty ◽  
Rajib Bhattacharjee ◽  
Shayani Bhanja ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Stable Disease ◽  
Immune Cells ◽  
Memory T Cells ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Potential Biomarker

e19040 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: 51 of selected pt.CD20+ DLBCL were treated with 6-8 cycles of R-CHOP and included in the present study. A panel of immune cells CD4+, CD8+ T cells, CD4+CD25+FoxP3 regulatory T cells, CD33+CD11b+CD14-/+ MDSCs and CD8+CD45RO+ Memory T cells were studied by flow-cytometry at different phases of treatment. Results: Within 51selected patients, 9 were disease free and 11patients exhibited stable disease for 2years (stable, non-relapsed, n = 20) following the completion of treatment. Rest of the patients (n = 31) showed relapse in different time periods within 2 years. Among several immune cells, CD33+CD11b+MDSCs were remarkably elevated in high grade residual and relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14- granulocytic, but not CD33+CD14+ monocytic MDSCs are mostly increased in relapsed patients than those having stable disease. CD4+CD25+FoxP3 regulatory T cells are also elevated in relapsed DLBCL patients, but increment is not comparable as MDSCs. No significant alteration was noticed in CD4+ and CD8+ T cells. Among relapsed patients CD8+CD45RO+ Memory T cells are increased, those are mostly corrupted in nature. Conclusions: Observed correlation between increased granulocytic MDSCs with the occurrence of residual disease and/or relapse suggests granulocytic MDSCs might be a potential biomarker for prediction of residual and relapse for DLBCL patients.

scholarly journals Tumor-associated myeloid-derived suppressor cells as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 30-30
Author(s):  
Kalyan KUSUM Mukherjee ◽  
Sukanya Dhar ◽  
Rajib Bhattacharjee ◽  
Subhadip Das ◽  
Mohona Chakraborty ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Cells ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Large Cell ◽  
Potential Biomarker ◽  
Cellular Components

30 Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: : Selected CD20+ DLBCL patients (n=51) were treated with 6-8 cycles of R-CHOP and included in the present study with their informed consent. A panel of immune cells, like, T (CD4+, CD8+)-cells, regulatory T (CD4+CD25+FoxP3)-cells, MDSCs (CD33+CD11b+CD14-/+), memory T (CD8+CD45RO+)-cells and multidrug resistance (MDR) phenotypes (P-gp, MRP1), were studied by flow-cytometry and RT-PCR at different phases of treatment. Results: Within 51 selected patients, 9 were disease free and 11 patients exhibited stable disease for 2 years following the completion of treatment. Rest of the patients (n=31) showed relapse in different time periods. Among several immune cells studied, CD33+CD11b+MDSCs were remarkably elevated in high-grade residual-and-relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14+ monocytic, but not CD33+CD14-granulocytic MDSCs were mostly increased in relapsed patients than control. Moreover, expression of MDR phenotypic markers was found to be elevated in these relapsed patients. Among relapsed patients CD8+CD45RO+ memory T cells were increased, however, these cells are mostly corrupted in nature. Conclusions: Observed correlation between increased monocytic MDSCs with the occurrence of residual disease and/or relapse suggests monocytic MDSCs might be a potential biomarker for prediction of residual-and-relapsed DLBCL patients.

scholarly journals Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma

2021 ◽  
Vol 14 (9) ◽  
pp. 101170
Author(s):  
Vera Bauer ◽  
Fatima Ahmetlić ◽  
Nadine Hömberg ◽  
Albert Geishauser ◽  
Martin Röcken ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals Myeloid-Derived Suppressor Cells Promote Cross-Tolerance in B-Cell Lymphoma by Expanding Regulatory T Cells

2008 ◽  
Vol 68 (13) ◽  
pp. 5439-5449 ◽  
Author(s):  
Paolo Serafini ◽  
Stephanie Mgebroff ◽  
Kimberly Noonan ◽  
Ivan Borrello
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Myeloid Derived Suppressor Cells ◽  
Cross Tolerance

scholarly journals High Levels of Regulatory T Cells in Blood Are a Poor Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma

2015 ◽  
Vol 144 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Chen Chang ◽  
Shang-Yin Wu ◽  
Yu-Wei Kang ◽  
Kun-Piao Lin ◽  
Tsai-Yun Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Depletion of CD4+  CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma

2008 ◽  
Vol 152 (2) ◽  
pp. 381-387 ◽  
Author(s):  
I. Heier ◽  
P. O. Hofgaard ◽  
P. Brandtzaeg ◽  
F. L. Jahnsen ◽  
M. Karlsson
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
B Cell ◽  
Tumour Growth ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Local Tumour

scholarly journals The number of tumour-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+ regulatory T cells predicts outcome in diffuse large B-cell lymphoma

2007 ◽  
Vol 137 (4) ◽  
pp. 364-373 ◽  
Author(s):  
Sverker Hasselblom ◽  
Margret Sigurdadottir ◽  
Ulrika Hansson ◽  
Herman Nilsson-Ehle ◽  
Börje Ridell ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Cytotoxic T Cells ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals CD19-CAR T Cells Treatment for Minimal Residual Disease in B-Cell Lymphoma with a Higher Response Rate and Fewer Adverse Reactions

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3714-3714
Author(s):  
Xia Xiao ◽  
Yanyu Jiang ◽  
Xiaoyuan He ◽  
Xin Jin ◽  
Cao Yaqing ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Response Rate ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Car T Cells ◽  
Car T ◽  
Minimal Residual

Abstract Background: Chimeric antigen receptor modified T cells directed against CD19 (CART19) has demonstrated efficacy in relapsed or refractory (r/r) B-cell lymphoma with durable complete remissions (CR). However, there are some patients with minimal residual disease (MRD) also need attention. Persistence or reappearance of minimal residual disease (MRD) after chemotherapy always results in relapse. MRD is an indicator of resistance to chemotherapy. Based on these considerations, a clinical retrospective trials with control and without random study (ChiCTR-ONN-16008911) was conducted to determine the efficacy and safety of CD19-CAR-T cells in MRD positive B-cell lymphoma patients, which is devoted to reduce the risk of recurrence. This paper will discuss the difference of efficacy and safety between minimal residual disease or partial remission and relapsed or refractory patients. The structural features of our CAR-T products include anti-CD19 scFv, a transmembrane domain, and a 4-1BB/CD3ζsignaling domain. Patients and Methods: This study enrolled B cell lymphoma in two cohorts. Cohort1 includes 10 patients with MRD persistence or reappearance after induction and consolidation therapy or patients acquired partial remission(PR). Cohort2 includes 12 patients with relapsed or refractory (r/r) B-cell lymphoma were included. We used autologous T cells expressing a CD19-CAR T cells to treat these patients. Patients were monitored for response to treatment, toxic effects, the expansion and persistence of CD19-CAR T cells. Results: 1. A total of 22 patients with B-cell lymphoma received CD19-CAR T cells, the median dose of CAR-T cells was 5.2×106/kg (2.0~10.0×106/kg). The infusions were safe, and no dose-limiting toxicities occurred. 2.The cohort1 overall response rate was 100%. Complete remission occurred in 8 of 10 patients (80%). The other 2patients with DLBCL were stable after CAR T cells treatment. The cohort2 overall response rate was 75%(9/12). Complete remission occurred in 2 of 12 patients (17%),partial remission occurredin 5 of 12 patients (42%).And another 2 patients got stable disease. 3. CD19-CAR T cells proliferated in vivo and were detectable in the blood of patients. The cohort1 and cohort2 peak time of CAR T cells proliferated was 12(5~19) days and 4.5(1~12) days after treatment respectively. And among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55% ~24.74%)and 4.02% (2.23%~28.60%) of T lymphocytes respectively. 4. The cohort1 patients achieved sustained remissions, and at a median follow-up of 10 months(3 ~18 months). None of all the patients relapsed and the median follow-up time was 10 months (3~18 months). However, 9 of the cohort2 patients who had a response maintain a good condition for 40-90 days. Except for one patient with following hematopoietic stem cell transplantation, the remaining patients developed disease progression in different degrees. 5. Cytokine-release syndrome(CRS) occurred in all patients, which in cohort1 were grade 1-2 CRS and in cohort 2 has one patient developed a grade 3 CRS. Conclusions: CAR-T cell therapy not only plays a role in the rescue treatment of relapsed and refractory patients, but also has a surprising effect in the consolidation and maintenance of B-cell lymphoma, and it is expected to become a treatment that benefits more patients.CD19-CAR T cells might be more effective in the treatment of MRD+/PR B-cell lymphoma patients than in the refractory or relapse patients. High response rate were observed, with fewer adverse reactions. CAR T treatment in MRD-positive B-cells lymphoma patients may be a therapeutic option to put off the progression to relapse and refractory lymphoma. Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of Tumor Infiltrating FOXP3 Positive Regulatory T Cells in Diffuse Large B-Cell Lymphoma at Diagnosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1565-1565
Author(s):  
Jae-Yong Kwak ◽  
Na-Ri Lee ◽  
Eun-Kee Song ◽  
Kyu Yun Jang ◽  
Ha Na Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Tumor infiltrating immune cells play an important role in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In the present study, we have identified a subset of tumor infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens and evaluated its prognostic significance. Ninety-six patients with DLBCL were retrospectively evaluated. Expression pattern of FOXP3 protein was examined using standard immunohistochemistry in paraffin-embedded tissue samples. The median overall survival (OS) was 28 months. Compared to the others, the patients with higher percentage of FOXP3-positive Tregs in the initial tumor biopsy, showed a significantly longer OS (p=0.003). When prognostic factors were evaluated in a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were shown to be independent predictors of OS. In conclusion, the presence of increased percentage of FOXP3-positive Tregs in DLBCL predicts a better prognosis. Figure Figure

Impact of Tumor Infiltrating T Cells in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1572-1572
Author(s):  
Shahryar Kiaii ◽  
Andrew James Clear ◽  
John G Gribben
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
B Cell ◽  
Immune Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treated Group ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1572 Previous studies have demonstrated the importance of the non-malignant tumor-infiltrating immune cells in the tumor microenvironment at diagnosis in patients with non-Hodgkin's lymphoma (NHL). We aimed to investigate the molecular mechanisms whereby tumor infiltrating T cells (TILs) are altered in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). We used gene expression profiling of highly purified CD4 and CD8 infiltrating T-cells (TILs) from FL patients and reported that PMCH, ETV1 and NAMPT are highly expressed in both CD4 and CD8 TILs and showed in tissue microarrays (TMA) that expression of pro-melanin-concentrating hormone (PMCH), ets variant 1 (ETV1) and nicotinamide phosphoribosyltransferase (NAMPT) in T-cells have prognostic impact in disease specific survivals (DSS) and time to transformation (TT) in patients with FL. In addition, PMCH and NAMPT were shown to be independently significant in TT in multivariate analysis. We next examined expression of these gene products in T cells in FL samples before and after transformation to DLBCL (n=29). Comparing total number of positive cells for expression of proteins of interest, we demonstrate there is a significant decline in PMCH (p=0.035), EVT1 (p=0.018) and NAMPT (p=0.0136) expressing cells after transformation. We further investigated the prognostic impact of expression of these proteins in T cells in patients with DLBCL in two treatment groups, those receiving rituximab (n=68) and in a historic non-rituximab (n=130) treated cohort. By assessing the number of positive cells and the impact on survival using Kaplan-Meier analysis, we now show that the T-cell expressed genes PMCH, ETV1 and NAMPT have prognostic significance for overall survival (OS) in patients with DLBCL. Patients with higher number of PMCH expressing T-cells showed significant longer survivals in both rituximab (p=0.027) and non-rituximab (p=0.033) treated groups. In contrast to PMCH, and in line with our previous data in FL, patients with higher number of NAMPT expressing cells showed significantly shorter OS in the rituximab (p=0.046) treated group, with a trend towards shorter OS in non-rituximab (p=0.064) treated group. Patients with higher percentage of ETV1 expressing cells had longer OS in the non-Rituximab group (p=0.008), with only a trend towards OS with rituximab treatment (p=0.067). We are examining this further in a larger cohort of rituximab treated patients. Our previous data has indicated that TILs in patients with FL are abnormal in terms of their gene expression and function. We now show that changes in protein expression in TILs have an impact on transformation in patients with FL and on survival in both FL and DLBCL. We are further characterizing the mechanisms of gene expression alteration in TILs of patients with FL and DLBCL and its functional consequences in the biology and of the disease. It appears that altered gene expression in TILs plays a fundamental role in transformation and may be important in the survivals and biology of NHL. Since non-malignant infiltrating immune cells have a crucial role in the outcome of patients with FL and DLBCL, understanding the nature and impact of the abnormalities induced in TILs in these patients is crucial before any immunotherapeutic strategies can be implemented to attempt to alter the immune microenvironment in NHL. Disclosures: Gribben: Celgene: Honoraria.

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