scholarly journals Dynamic changes in peripheral blood lymphocyte subset counts and functions in patients with diffuse large B cell lymphoma during chemotherapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hongyan Hou ◽  
Ying Luo ◽  
Guoxing Tang ◽  
Bo Zhang ◽  
Renren Ouyang ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
B Cell ◽  
Lymphocyte Subsets ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Dynamic Changes ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background This study aimed to analyze the lymphocyte subsets, their activities and their dynamic changes during immunochemotherapy in patients newly diagnosed with diffuse large B cell lymphoma (DLBCL). Methods Patients with DLBCL (n = 33) were included in the present study. Their peripheral lymphocyte subsets, phenotypes and functions were detected using flow cytometry. The dynamic results of lymphocyte activities were available for 18 patients. Results Compared with healthy controls (HCs), the counts of CD3+, CD4+, and CD8+ T cells as well as those NK cells decreased in patients newly diagnosed with DLBCL, mainly attributed to patients with high risk of prognosis assessed by International Prognostic Index (IPI) score. Lymphocyte counts didn’t present significant difference between high risk (IPI scores 3–5) and low risk patients (IPI scores 0–2), but CD4+ T cells and CD8+ T cells expressed higher levels of CD28 and HLA-DR, respectively, in patients with IPI score ranging from 3 to 5. Patients at high risk harbored higher percentage of regulatory T cells (Tregs), and their CD4+ and CD8+ T cells produced lower levels of IFN-γ, reflecting an impaired cellular immune response. The dynamic changes of lymphocyte numbers and functions during treatment were further investigated. Total counts of CD3+, CD4+, CD8+ T and NK cells progressively decreased because of the cytotoxicity of chemotherapy and then gradually recovered after six cycles treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). The functions of CD4+ and CD8+ T cells recovered by the end of two cycles R-CHOP treatment, although NK cell function was not significantly affected throughout treatment. These results suggest that the counts and functions of lymphocytes are significantly decreased in patients with DLBCL, particularly those of CD4+ and CD8+ T cells. Conclusions The absolute counts and functions of CD4+, CD8+ T cells, which were significantly lower in patients with DLBCL, gradually recovered after effective treatment. Therefore, combined detection of T cell counts and functions are critically important for administering effective personalized immunotherapy as well as for identifying new prognostic markers or DLBCL.

Prognostic Impact of Peripheral Blood T-Cell Subsets at the Time of Diagnosis on Survival in Patients with Diffuse Large B-Cell Lymphoma

2020 ◽  
pp. 1-11
Author(s):  
Ho-Jin Shin ◽  
Do-Young Kim ◽  
JooSeop Chung ◽  
Kyung-Hwa Shin ◽  
Hyungi Lee
Keyword(s):  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Th Cells ◽  
Large B Cell Lymphoma ◽  
Large B Cell

<b><i>Introduction:</i></b> The effects of lymphocyte subtypes, including helper (Th), natural killer (NK), and regulatory (Treg) cells, and other T-cell subtypes on treatment outcomes in diffuse large B-cell lymphoma (DLBCL) patients are not clearly established. <b><i>Methods:</i></b> Among 151 consecutive patients diagnosed with DLBCL, we collected peripheral blood samples at diagnosis from 91 patients who received at least 1 cycle of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) chemotherapy and analyzed lymphocyte subsets by flow cytometry. <b><i>Results:</i></b> DLBCL patients had a higher proportion of CD4<sup>+</sup>CD25<sup>+</sup> Treg (<i>p</i> &#x3c; 0.001) and lower absolute lymphocyte count than those of healthy controls. Lymphopenia at diagnosis was associated with advanced-stage disease (<i>p</i> = 0.001), a high-intermediate/high-risk International Prognostic Index (IPI) (<i>p</i> &#x3c; 0.001), and older age (<i>p</i> = 0.060). High-intermediate/high-risk IPI, high proportion of CD3<sup>+</sup>CD4<sup>+</sup> Th cells, and extranodal site ≥2 correlated with unfavorable prognostic factors for survival. High proportion of Th cells was associated with fewer cytotoxic T cells and NK cells at the time of diagnosis. <b><i>Conclusion:</i></b> This study showed an association between circulating lymphocyte subsets including Th cells, Tregs, and NK cells and clinical outcomes in DLBCL; however, further confirmation is needed via prospective trials.

scholarly journals Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Selin Merdan ◽  
Kritika Subramanian ◽  
Turgay Ayer ◽  
Johan Van Weyenbergh ◽  
Andres Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
B Cell ◽  
Risk Prediction ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Signatures ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractThe clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

scholarly journals Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients

2021 ◽  
Vol 10 (8) ◽  
pp. 1768
Author(s):  
Zhitao Wang ◽  
Rui Jiang ◽  
Qian Li ◽  
Huiping Wang ◽  
Qianshan Tao ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Pathological Process ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Accumulation Mechanism ◽  
Large B Cell

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.

scholarly journals Use of immune repertoire sequencing to resolve discordant microscopic and immunochemical findings in a case of T cell-rich large B cell lymphoma in a young dog

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Gary Kwok Cheong Lee ◽  
Dorothee Bienzle ◽  
Stefan Matthias Keller ◽  
Mei-Hua Hwang ◽  
Nikos Darzentas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Repertoire ◽  
Large B Cell Lymphoma ◽  
Repertoire Sequencing ◽  
Reactive Lymphocytes ◽  
Large B Cell

Abstract Background Lymphocytic neoplasms with frequent reactive lymphocytes are uncommonly reported in dogs, and can pose a diagnostic challenge. Different diagnostic modalities such as cytology, flow cytometry, histopathology, immunohistochemistry, and clonality testing, are sometimes required for a diagnosis. This report illustrates the value of using a multi-modal diagnostic approach to decipher a complex lymphocytic tumor, and introduces immune repertoire sequencing as a diagnostic adjunct. Case presentation A 10-month-old Great Dane was referred for marked ascites. Cytologic analysis of abdominal fluid and hepatic aspirates revealed a mixed lymphocyte population including numerous large lymphocytes, yielding a diagnosis of lymphoma. Flow cytometrically, abdominal fluid lymphocytes were highly positive for CD4, CD5, CD18, CD45, and MHC II, consistent with T cell lymphoma. Due to a rapidly deteriorating clinical condition, the dog was euthanized. Post mortem histologic evaluation showed effacement of the liver by aggregates of B cells surrounded by T cells, suggestive of hepatic T cell-rich large B cell lymphoma. Immune repertoire sequencing confirmed the presence of clonal B cells in the liver but not the abdominal fluid, whereas reactive T cells with shared, polyclonal immune repertoires were found in both locations. Conclusions T cell-rich large B cell lymphoma is a rare neoplasm in dogs that may be challenging to diagnose and classify due to mixed lymphocyte populations. In this case, the results of histopathology, immunohistochemistry and immune repertoire sequencing were most consistent with a hepatic B cell neoplasm and reactive T cells exfoliating into the abdominal fluid. Immune repertoire sequencing was helpful in delineating neoplastic from reactive lymphocytes and characterizing repertoire overlap in both compartments. The potential pitfalls of equating atypical cytomorphology and monotypic marker expression in neoplasia are highlighted.

Sign in / Sign up

Export Citation Format

Share Document