Tumors that look for their springtime in APRIL
Section snippets
APRIL and its multiple receptors
A proliferation inducing ligand (APRIL, TNFSF-13) is one of the most recently cloned members of the tumor necrosis factor (TNF) superfamily [1], [2]. APRIL is closely related to another member of the TNF family, the B-cell activation factor (BAFF, TNFSF-13B). Although some BAFF and APRIL functions are similar [3], most of their functions are non-redundant, which is best illustrated by the distinct phenotype of BAFF- and APRIL-deficient mice [4], [5], [6]. Furthermore, BAFF has a unique
APRIL production and tissue distribution
Early Northern blot studies performed shortly after its cloning reported that APRIL is broadly expressed in diverse tissues, with a high expression in peripheral blood and an intermediate expression in pancreas, small intestine, protaste and ovary [1]. APRIL mRNA was observed in hematopoietic cells from the myeloid lineage [33], but also in megakaryocytes [34], osteoclasts [35], and mesenchymal cells [36]. Furthermore, APRIL mRNA was detected in tumor cells from diverse origins such as solid
Solid tumors
APRIL was originally described as a factor promoting solid tumor development in an autocrine fashion [1], [2], [37]. Its tumor-promoting capacity was shown in vitro by addition of recombinant APRIL to tumor cells [2], and in vivo either by APRIL transfection into tumors [2], or by antagonizing endogenous APRIL [45]. However, the identification of BCMA and TACI that are mainly expressed by B cells [46] as the receptors for APRIL raised doubts on the tumor-promoting role for solid tumors. At
APRIL and tumors at the bedside
Several studies investigated to what extent the survival and/or proliferation signals given by APRIL to tumor cells in experimental models would impact tumor development in patients. Obviously, the tumor-promoting effect of APRIL signaling may be reduced in patients under treatment. The role of APRIL in the clinical outcome of patients was recently studied by two different approaches. In the first approach, APRIL was quantified by immunohistochemistry in biopsies of tumor lesions. The results
Concluding remarks
The inflammatory cytokine APRIL is abundantly present in lesions from diverse tumors and implicated in the natural growth of many tumors, consistent with the current concept that inflammatory reactions constitute an important part of a tumor development. The impact of APRIL on tumor development is likely to depend on the nature of the APRIL-R expressed by tumor cells, with the lowest impact for solid tumors only expressing HSPG, and the highest for B-cell lymphoid neoplasias expressing HSPG but
Reviewers
Prof. Jan Paul Medema, Amsterdam Medical Center, Laboratory of Experimental Oncology and Radiology, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
Dr. Yataro Yoshida, Takeda Sogo Hospital, Department of Hematology, Fushimi-ku, Kyoto, Japan.
Acknowledgements
The authors thank Dr. Henri Dubois-Ferrière/Dinu Lippatti foundation, the Swiss National Science Foundation, the Leenaards foundation and the Jacques und Gloria Gossweiler Stiftung for their financial support.
Eddy Roosnek is a Ph.D. He is currently leading a research group in the Hematology unit from the Geneva University Hospital.
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B Cells and Regulatory B Cells in Cancer Escape
2016, Encyclopedia of ImmunobiologyGranulocytes: Neutrophils, Basophils, Eosinophils
2013, The Autoimmune Diseases: Fifth EditionOn the cytokines produced by human neutrophils in tumors
2013, Seminars in Cancer BiologyCitation Excerpt :APRIL-transgenic mice develop a B-1-cell associated neoplasia, which is reminiscent of human B chronic lymphocytic leukemia (B-CLL) [25]. Besides being broadly expressed in normal tissue and tumor cells from diverse origin [26], APRIL has been also detected in peripheral blood neutrophils from healthy subjects at both mRNA and protein levels [27], as well as in neutrophils infiltrating human mucosa-associated lymphoid tissue (MALT) [28]. Most of the evidence suggesting a role for neutrophils as a source of APRIL in normal and neoplastic tissues derive from in situ studies in which two specific anti-APRIL antibodies, discriminating APRIL-binding (Aprily-2) and APRIL-producing cells (Stalk-1), were used [27].
Neoplastic " Black Ops": Cancer's subversive tactics in overcoming host defenses
2012, Seminars in Cancer BiologyCitation Excerpt :The non-metastatic cancer subsets also express B cell survival factor BAFF to actively maintain tBregs. In fact, BAFF and APRIL (a proliferation-inducing ligand) can be found expressed in human solid tumors, including breast carcinomas [158,159], suggesting an interesting possibility that these factors also support survival of tBregs in humans. So far, tBreg-like cells have been in vitro generated from normal human donor B cells treated with conditioned media of human cancer lines, such as breast, ovarian and colon carcinomas [40].
Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma
2011, BloodCitation Excerpt :Notably, a fraction of APRIL-positive macrophages contain HP-derived products; moreover, in vitro HP infection induces expression of APRIL in monocyte-derived macrophages, thus indicating a primary role of the bacterium in promoting monocyte-derived cells to produce APRIL in infected gastric mucosa. A large body of experimental and clinical evidence suggest that APRIL sustains B-cell transformation and progression of B-cell lymphomas.11-14 Different forms of B-cell lymphoma were found to contain APRIL-positive cells, that were represented either by neoplastic B-cells and by tumor associated immune cells,13 including macrophages.22
B cell‐activating factors in autoimmune pulmonary alveolar proteinosis
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Eddy Roosnek is a Ph.D. He is currently leading a research group in the Hematology unit from the Geneva University Hospital.
Maka Burjanadze obtained his Ph.D. in 2007 from the Montpellier University in France. She joined recently the group of Bertrand Huard.
Pierre-Yves Dietrich is a M.D. He is professor in the Oncology department from the Geneva University Hospital.
Thomas Matthes is a M.D. He is currently leading a research group from the Hematology unit in the Geneva University Hospital.
Jakob Passweg is a M.D. He is currently leading the Hematology unit from the Geneva University Hospital.
Bertrand Huard is a Ph.D. He is currently leading a research group from the Hematology unit in the Geneva University Hospital.