59 research outputs found
Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond
Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children
but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody–drug conjugates, chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients
Pulmonary function testing for fitness assessment in asymptomatic adults with newly diagnosed acute myeloid leukemia
Not available
Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment
The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked toCD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells
recognized three breast cancer (BC) and one colon cancer cell line
among 15 tested in the absence of targeting antibodies. Sensitive
BC cell conjugation with CD32-CR T cells induced CD32 polarization
and down-regulation, CD107a release, mutual elimination,
and proinflammatory cytokine production unaffected by human
IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient
mice from subcutaneous growth of MDA-MB-468
BC cells. RNAseq analysis identified a 42 gene fingerprint predicting
BC cell sensitivity and favorable outcomes in advanced BC.
ICAM1 was a major regulator of CD32-CR T cell–mediated cytotoxicity.
CD32-CR T cells may help identify cell surface CD32 ligand(s)
and novel prognostically relevant transcriptomic signatures and
develop innovative BC treatments
Case report: A Saprochaete clavata (Magnusiomyces clavatus) severe infection effectively treated with granulocyte transfusion in a young patient with myeloid sarcoma
Myeloid sarcoma is a hematologic malignancy consisting of extramedullary
tissue involvement by myeloid blasts, usually considered as acute myeloid
leukemia and treated accordingly. The disease itself, together with
chemotherapy and disease-associated factors, may have an impact in
increasing the risk of developing severe and frequently life-threatening
infections. Herein, we describe the case of a patient with a right breast skin
lesion, histologically diagnosed myeloid sarcoma, who developed a severe
disseminated fungal infection by Saprochaete clavata (Magnusiomyces
clavatus), during the first consolidation course of chemotherapy. Despite
maximum antifungal therapy, the infection progressed and the fungus
continued to be isolated until granulocyte transfusion therapy was initiated.
Our experience suggests that patients with profound and long-lasting
neutropenia could benefit from granulocyte transfusions as additional
therapy in severe fungal infections resistant to broad-spectrum
antimicrobial therapy
Recommended from our members
Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage
Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells
Glioma extracellular vesicles for precision medicine: prognostic and theragnostic application
EV produced by tumour cells carry a diverse population of proteins, lipids, DNA, and RNA molecules throughout the body and appear to play an important role in the overall development of the disease state, according to growing data. Gliomas account for a sizable fraction of all primary brain tumours and the vast majority of brain malignancies. Glioblastoma multiforme (GBM) is a kind of grade IV glioma that has a very dismal prognosis despite advancements in diagnostic methods and therapeutic options. The authors discuss advances in understanding the function of extracellular vesicles (EVs), in overall glioma growth, as well as how recent research is uncovering the utility of EVs in glioma diagnostics, prognostic and therapeutics approaches
High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor
BACKGROUND
Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG).
METHODS
A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets.
RESULTS
MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-.
CONCLUSIONS
High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC
Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients
Tumor associated antigens are useful in colorectal cancer (CRC) management. The ribosomal P proteins (P0, P1, P2) play an important role in protein synthesis and tumor formation. The immunogenicity of the ribosomal P0 protein in head and neck, in breast and prostate cancer patients and the overexpression of the carboxyl-terminal P0 epitope (C-22 P0) in some tumors were reported
- …