This study was aimed to investigate the therapy and prognostic factors of angioimmunoblastic T cell lymphoma (AITL). The clinical data of 23 patients with AITL were collected and the clinical features, laboratorial data, survival and prognostic factor were retrospectively analyzed. The results indicated that the median age of the patients was 62 years. Out of them 21 (91.3%) patients were with intermediate high and high risk according to the international prognostic index (IPI), 14 (60.9%) patients had extranodal disease and 5 (21.7%) patients had autoimmune disease. The overall response rate(ORR) for the whole group was 68.2%, the estimated 3-year and 5-year survival rates were 38.3% and 28.7% respectively. High-dose chemotherapy combined with auto-HSCT improved the outcome of young patients. Immunosuppressive therapy were used in replace/refractory patients. Age more than 65 years, IPI score, LDH level, the number of lymph node involvement, short-term effect, fibrinogen level, β2-MG level and bone marrow involvement were prognostic factors with statistical significance. Cox multivariate analysis showed that the level of LDH, β2-MG and bone marrow involevment were independent prognostic factors, IPI, PIT and mPIT were useful for stratified patients into different prognostic risk groups. It is concluded that AITL is aggressive disease occurred in older patients, and autoimmune dysfunction with infectibility, often appears in AITL patients with poor prognosis. The young patients can be benefited from initial intensive chemotherapy. High-dose chemotherapy combined with auto-HSCT may be a better choice for those patients. Immunosuppressive therapy can be used in replase/refractory patients.
Humans ; Lymphoma, T-Cell ; diagnosis ; immunology ; Prognosis ; Retrospective Studies

Fatal Outcome ; Humans ; Inflammation ; immunology ; metabolism ; mortality ; Lymphoma, T-Cell ; immunology ; metabolism ; mortality ; Male ; Middle Aged

Apoptosis ; Cell Line, Tumor ; Humans ; Immunophenotyping ; Killer Cells, Natural ; immunology ; Lymphoma, T-Cell ; immunology ; pathology ; Nose Neoplasms ; immunology ; pathology

OBJECTIVETo identify the clinical and pathological features of natural killer-like T-cell lymphoma/leukemia.

METHODSThe characteristics of natural killer-like T-cell lymphoma/leukemia was discussed with report a new case and review of literatures.

RESULTSA 16-year-old girl was referred to our hospital because of fever and disseminated cutaneous herpes and ulcer. Atypical lymphoid cells surrounded the dermal vessels with a CD3(+), CD8(+), CD4(-), CD5(-), CD10(-), CD19(-), CD57(-), CD56(+), perforin(+), granzyme B(+) immunophenotype and rearranged T-cell receptor-gamma gene implicated natural killer-like T cell origin. She was treated with prednisone and for several months. Then the patient developed progressive spleen enlargement with overt leukemia, which led to her eventual death.

CONCLUSIONSNatural killer-like T-cell lymphoma/leukemia is a rare disease with distinctive clinical, histopathologic, and immuno phenotypic characteristics. Current treatment modalities are ineffective for most of the patients.

Adolescent ; CD56 Antigen ; immunology ; Female ; Humans ; Killer Cells, Natural ; immunology ; pathology ; Leukemia, T-Cell ; immunology ; pathology ; Lymphoma, T-Cell ; immunology ; pathology

Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.
Animals ; Humans ; Immunity, Cellular ; Immunotherapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; pathology ; therapy ; Receptors, Antigen, T-Cell ; immunology ; Recombinant Fusion Proteins ; immunology ; T-Lymphocytes ; immunology ; transplantation

OBJECTIVETo investigate the clinical significance of peripheral blood regulatory T cell (Treg) population in patients with extranodal NK/T cell lymphoma, nasal type (ENKL).

METHODSThe peripheral blood CD4+CD25+ Treg cell population was detected by flow cytometry in 41 newly diagnosed ENKL patients between March 2009 and December 2012.

RESULTSThe proportion of CD4+CD25+ Treg cell population increased in ENKL patients compared to healthy donors [(9.64±4.96)% vs(7.31±3.02)%, P<0.05], and decreased significantly after treatment [(5.18±2.19)%, P<0.01]. Patients when got response had significantly lower proportion of Treg cells [(8.79±4.15)%] as compared with those without response [(14.57±6.73)%, P<0.05]. The proportion of Treg population was positively related to the serum lactate dehydrogenass level.

CONCLUSIONThe proportion of peripheral blood Treg cells may be helpful for predicting prognosis and therapeutic efficacy in ENKL patients.

CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; Flow Cytometry ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; Lymphoma, T-Cell ; diagnosis ; immunology ; Prognosis

Over a two-year period, immunophenotypic patterns of 266 acute leukemia cases were analyzed using a panel of tests including TdT, SmIg and 9 surface antigens by the immunofluorescence stains for the assessment of the incidence and grade of phenotypic ambiguity (lineage infidelity) and the possible clinical significance of unusual immunophenotypes. Immunophenotypes were classified into four groups according to the degree of ectopic antigen expression. We classified as Group A (91.7%, 244 of 266 cases) those expressing conventional pattern without ectopic antigen. Group B (3.0%, 8 of 266 cases) was defined to have at least two lineage specific markers and single ectopic antigen. Such a "low grade deviation" did not prevent a definite immunodiagnosis. Group C (4.2%, 11 of 266 cases) revealed a promiscuous coexpression of markers related to different lineages, including two cases (0.8%, 2 cases) of biphenotypic leukemia. Group D (1.1%, 3 cases) included unclassifiable immunophenotypes with no antigen or HLA-DR only expression. Both patients with biphenotypic leukemia and one patient with unclassifiable immunophenotypes failed to respond to induction chemotherapy, suggesting a poor prognosis in these patients. The incidence of acute myelogenous leukemia (AML) cases with one or more ectopic surface antigens was 10 (8.1%) of the 124 AML cases. Ectopic antigen expression was seen in 5 (4%) of the 125 B-lineage acute lymphoblastic leukemia (ALL) cases and 3 (25%) of the 12 T-ALL cases. It is concluded that nearly 95% of cases of acute leukemia cases can be diagnosed accurately with immunophenotyping alone including patients with a mild degree of deviation from expected antigenic patterns.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease ; Antigens, Differentiation/blood ; Burkitt Lymphoma/immunology ; Humans ; Immunophenotyping ; Leukemia/*immunology ; Leukemia, Myeloid/immunology ; Leukemia-Lymphoma, Adult T-Cell/immunology ; Retrospective Studies

After having successfully constructed and expressed the gene of the anti-CD3/anti-CD20 bispecific single-chain antibody (bscCD3 x CD20), here we analyzed its in vitro bioactivity of mediating the lysis of Ramous human B-lymphoma cells in the presence of T-enriched human peripheral blood lymphocytes (PBL). Obvious opoptosis characters were observed by Annexin V/PI(AV/PI) stained and scanning electron microscope. As evaluated by non-radioactive cytotoxity assay, the bscCD3 x CD20 showed potent bioactivity of mediating human B-lymphoma cells lysis in the presence of T-enriched human PBL. The potency of cytotoxicity depended on the ratios of effect cells to target cells (E:T) used. Further, the antibody showed a dose and time-dependent effect on mediating Ramous cells lysis. The specific lysis reached about 87.3% at an antibody concentration of 5microg/mL and E:T used at 10:1. Clear changes in apoptogenes expression profiles were detected by apoptosis gene array after Ramous cells were treated with the antibody and PBL. Among the upregulated apoptogenes, ATM and P53 showed an increase of 187 times and 15 times respectively, which suggested that ATM-p53 pathway may be the main apoptosis way of Ramous cells induced by T cells in the presence of the bscCD3 x CD20.
Antibodies, Bispecific ; immunology ; Antigens, CD20 ; immunology ; Apoptosis ; immunology ; CD3 Complex ; immunology ; Humans ; Lymphoma, B-Cell ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Cells, Cultured

Aneuploidy ; DNA, Neoplasm ; analysis ; genetics ; Flow Cytometry ; methods ; Humans ; Lymphoma ; diagnosis ; genetics ; immunology ; Lymphoma, B-Cell ; diagnosis ; genetics ; immunology ; Lymphoma, T-Cell ; diagnosis ; genetics ; immunology ; Receptors, Antigen, T-Cell ; analysis ; genetics

OBJECTIVETo identify immune epitopes existed in the framework region (FR) of the IgHV protein of B-cell malignance, and explore the use of these FR-derived peptides to induce the family specific immune response in vitro, in order to explore the possibility of a new IgHV gene family-specific immunotherapy for B-cell malignance.

METHODSBioinformatics was used for predicting T cell epitopes in IgHV protein. Peptides of interest were synthesized in vitro. T2 cell binding assay was performed to determine the binding ability of the peptides to HLA-A*0201 molecules. Peptide/HLA tetramer staining was used to detect the number of peptide-specific cytotoxic T lymphocytes (CTLs). Cytotoxicity assay was used to determine killing activity.

RESULTSTwelve peptides that were common to seven IgHV gene subfamilies were identified, and 10 (83%) of them were located in the FR of IgHV protein. The synthesized peptides up-regulated HLA*0201 molecules fluorescence intensity on cell surfaces of T2. By using an antigen-specific T-cell expansion system in vitro, the peripheral blood mononuclear cells (PBMNC) from a healthy HLA-A0201 donor were stimulated weekly by autologous PBMNC loaded with the peptide as antigen presenting cells (APC), and the peptide-specific CTLs were demonstrated to be generated successfully in the healthy donors. The frequency of CD8 and peptide/HLA tetramer double positive cells in the gated lymphocyte population was 0.38% before stimulation and increased to 49.38 % after four times stimulation. Cytotoxicity assay indicated that these CTLs were capable of killing the HLA-A*0201, IgHV1 (+) lymphoma cells. Furthermore, the generated CTL could not kill the target cell loaded with the IgHV3 peptide, indicating that the cytotoxicity is family-specific.

CONCLUSIONPeptides derived from the IgHV protein FR can successfully induce the generation of peptide-specific CTLs in vitro. These CTLs are capable of killing the lymphoma cell belonged to the same subfamily in a peptide-specific and MHC-restricted way. These findings could potentially form the basis of broadening application of immunoglobulin-directed immunotherapy in B-cell malignancies.

Cells, Cultured ; Epitopes, B-Lymphocyte ; immunology ; Humans ; Immunoglobulin Heavy Chains ; immunology ; Immunoglobulin Variable Region ; immunology ; Lymphoma, B-Cell ; immunology ; T-Lymphocytes, Cytotoxic ; immunology