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Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Therapeutic strategies should ideally be commensurate to individual patient and disease characteristics, in the presence or absence of co-morbidities. Definitive treatment often includes rituximab or ofatumumab, in combination with bendamustine, cladribine, bortezomib or ibrutinib. It accords control of the disease, but no overall survival advantage. In relapsed and refractory disease, it is reasonable to consider high-dose chemotherapy and auto-SCT in chemosensitive patients. Investigational agents include BTK and TLR inhibitors, mTOR inhibitors, ofatumumab, a fully humanized monoclonal anti-CD20 antibody, CXCR4 antagonists such as plerixafor and a host of targeted therapies against MY88, BCL2 and CD27/CD70 signalling pathways. There is also some interest in testing adoptive cellular immunotherapy treatments, including CAR T-cell therapy.
Lupus erythematosus syndrome induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
One concern about these studies is that the immunopathological features of this mouse model do not resemble DIL but are more like the global autoimmune characteristics of a graft-versus-host reaction when adoptively transferred semi-allogeneic T-cells recognize histoincompatible MHC molecules in the host.65 This syndrome is similar to SLE, while DIL displays much more limited autoimmune features (see Table 27.1). In addition, since multiple exposures to large numbers of dividing lymphocytes were required to produce the in-vivo phenomena, it is not clear what the natural counterpart of such a polyclonal T-cell activation would be. Immune responses to infectious agents that might occur coincident with medication with a lupus-inducing drug would be expected to be associated with a much more limited, oligoclonal T-cell activation. However, it is possible that, in DIL, autoreactive T-cells developing through another mechanism become more aggressive owing to such a drug-induced LFA-1 and/or CD70 over-expression process, thereby aggravating disease in DIL.
Intraepithelial T cells: Specialized T cells at epithelial surfaces
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Activation of transferred OT-I transgenic cells by feeding soluble ovalbumin does not induce lytic activity in nonintestinal OT-I cells, but upon migration into the intestinal mucosa these cells become highly lytic. Moreover, optimal activation of mucosal T cells requires B7.1, and CD40L expressed by CD8αβ+ T cells is important for optimal expansion of mucosal CD8αβ+ T cells in response to virus infection. Similarly, CD70–CD27 and CD40–CD40L costimulation appears to be important for expansion of CD8αβ+TCRαβ+ iIETs after oral Listeria monocytogenes infection, presumably for “secondary” costimulation, since lymphoid tissue is required for initial priming. These observations indicate that tissue-specific cellular interactions further condition the iIETs resulting in tuning of their effector phenotype and function. In this light, and similarly to the nIETs, a large fraction of iIETs express CD8αα as part of their specific adaptation to the epithelial compartment. Although most memory CD8αβ iIETs retain an activated phenotype (e.g., CD69 expression and a heightened cytolytic state) that enables them to rapidly respond to antigen reexposure, they also display reduced ability to proliferate and to produce inflammatory cytokines typical of effector memory T cells. In this respect, intestinal CD8αβ and also CD8αα T cells express high levels of the P2X7 purinoreceptor, which is induced by retinoic acid in the gut environment. Similar to the TL-mediated selective maintenance of only the high-affinity CD8 effector memory iIETs, intestinal effector T cells can also be deleted by P2X7 activation-dependent apoptosis. The retinoic acid-P2X7 axis limits excessive buildup of activated T cells and thereby controls intestinal homeostasis.
Targeting myeloid cells with bispecific antibodies as novel immunotherapies of cancer
Published in Expert Opinion on Biological Therapy, 2022
Celine A.N. Sewnath, Leonie M. Behrens, Marjolein van Egmond
Instead of targeting CD47, BsAbs that are directed against SIRPα have also been developed. Human CD70 is an antigen that is overexpressed in several malignancies, such as non-Hodgkin lymphoma, multiple myeloma, renal carcinoma, and glioblastoma [96,97]. Phagocytosis of various renal carcinoma cell lines, including RCC4, RCC10, TK10, and CAKi-1 by macrophages was significantly enhanced in the presence of 10 µg/ml CD70xSIRPα BsAbs in vitro, which was not observed in the presence of anti-SIRPα or anti-CD70 mAbs alone [98]. Furthermore, treatment with 10 mg/kg CD70xSIRPα BsAbs reduced human Burkitt’s lymphoma cell growth in immunodeficient mice, which was comparable to co-treatment with anti-SIRPα and anti-CD70 mAbs. In summary, targeting either CD47 or SIRPα with BsAbs can stimulate macrophages, which may lead to enhanced eradication of tumor cells.
DNA Methylation of CD70 Promoter in Juvenile Systemic Lupus Erythematosus
Published in Fetal and Pediatric Pathology, 2022
Mahsa Keshavarz-Fathi, Golshid Sanati, Maryam Sadr, Bahareh Mohebbi, Vahid Ziaee, Nima Rezaei
Expression of CD70 accounts for proliferation of T-cells and increased survival of antigen specific CD8+ T-cells through reinforcement of secretion and function of IL-2 [32]. A contrary effect was observed in the function of B-cell. Activity of CD27 signaling on both B-cell and T-cell fosters formation of germinal center and production of IgG [33]. However, constitutive expression of CD70 on B-cell hampers the number of B-cells and production of IgG through CD27 signaling, which induces production of IFN-γ [34,35]. There is an auto-regulatory system determining expression of CD70. Coupling of CD27 and CD70 leads to decreased expression of CD70. Increased expression of CD70 was observed in a study of CD27 deficient animals or by blockade of this interaction utilizing a monoclonal antibody [36].
Emerging pharmacotherapies for elderly acute myeloid leukemia patients
Published in Expert Review of Hematology, 2020
Xavier Thomas, Mohamed Elhamri, Maël Heiblig
CD70 is a cell surface antigen normally expressed by activated B- and T-lymphocytes and mature dendritic cells [164]. CD70 is involved in lymphocyte differentiation and survival signaling upon binding to its cognate cell surface receptor, CD27 [165]. CD70 and CD27 are overexpressed in hematological malignancies including AML, suggesting their involvement in malignant cell proliferation and survival [164]. Both antigens are expressed by leukemic stem cells (LSCs). Binding of CD70 to CD27 activates the NF-κB pathway resulting in proliferation and survival of malignant cells and to the cleavage of CD27 leading in soluble CD27 (Figure 8). CD70 also plays a role in the evasion of immune surveillance by inducing T cells with regulatory potential promoting tumor growth [166].