Involvement Of Mast Cells Research Articles

Mast cells: new therapeutic target in helminth immune modulation.

Helminth infection and their secreted antigens have a protective role in many immune-mediated inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. However, studies have focused primarily on identifying immune protective mechanisms of helminth infection and their secreted molecules on dendritic cells and macrophages. Given that mast cells have been shown to be implicated in the pathogenesis and progression of many inflammatory disorders, their role should also be examined and considered as cellular target for helminth-based therapies. As there is a dearth of studies examining the interaction of helminth-derived antigens and mast cells, this review will focus on the role of mast cells during helminth infection and examine our current understanding of the involvement of mast cells in TH 1/TH 17-mediated immune disorders. In this context, potential mechanisms by which helminths could target the TH 1/TH 17 promoting properties of mast cells can be identified to unveil novel therapeutic mast cell driven targets in combating these inflammatory disorders.

Impact of vitamin D on asthma

Asthma is a chronic inflammatory disease of the lung of atopic individuals with an acute intermittent reversible obstructive airway disease [1]. This leads to wheeziness, chest tightness, obstruction of the lumen of the lower respiratory tract, bronchospasm, edema, thick secretions, accumulation of inflammatory cells [including mast cells and eosinophils] and hyperplasiahypertrophy of the smooth muscle and mucus secretion, exacerbating respiratory difficulties [1]. There are two major asthma types, allergic and non-allergic, with similar manifestations of inflammation and airway hyper-responsiveness, mediated by different mechanisms. By definition, allergic asthma is associated with allergensesitization, IgE-mediated hypersensitivity and Type2 immune responses (Th2-cells); while non-allergic asthma is associated with a neutrophilic inflammatory response and a Type1 (Th1-cells) and Type-17 (Th17-cells) cytokine profile. About 70% of cases of asthma involve mast cell reactions, mainly due to IgEmediated immediate hypersensitivity [2]. The number of cases and severity of asthma have been increasing without any plausible explanation. A large number of reports indicated that the pathophysiology of asthma is initiated by mast cell activation in response to allergen binding IgE receptor and TH2-cells [3]. This leads to cytokine generation by the mast cells and recruitment of eosinophils and

Mast cell activation syndrome.

It has been over 30 years since the Interstitial Cystitis Association of America (ICA) was established in 1984. Although a great deal more is understood about interstitial cystitis/bladder pain syndrome (IC/BPS), the cause and cure of this condition remains unknown. One hypothesis regarding etiology that appears to have been overlooked or dismissed is a theory that involves mast cells. It is worthwhile taking a second look.

Density of Tryptase-Positive Mast Cells Correlated with the Presence of H. pylori in Gastric Neoplasia.

Gastric cancer continues to be a platoon leader of mortality causes. A significant number of recent studies show direct or indirect involvement of mast cells (MC), with a complex role both pro- and anti-tumor growth. To objectify the correlations between expression of MC and presence of Helicobacter pylori (HP) infection depending on neoplastic nature of the gastric damage. The study was carried out on archival samples of gastric wall from 30 patients with gastric cancer versus 30 age and sex-matched subjects with gastric surgery for non-neoplastic diseases. The inclusion criteria for the case group were histologically proven stage T3/T4 malignancies with regional lymph node metastases. For each case of the study group, distribution and number of MC tryptase positive (DMC-TP) were analyzed in five different areas from the same gastrectomy specimen: intratumor area, deep and side tumor invasion front, normal gastric tissue sample 5-10 cm or more distant from the tumor and furthest resection margin. Independently of HP infection, the study recorded a significantly lower value of DMC-TP in male patients. In regions with inflammatory lesions and preneoplastic changes and in control cases with non-gastric neoplasia, the DMC-TP level was higher than controls with HP-related inflammatory pathology, thus removing bacterial etiology from the forefront of MC mobilizing causes. The presence of H. pylori infection was not found to cause significant changes in terms of mobilizing mast cells in the gastric wall with advanced tumors, with minimal stage III TNM.

Mast cell involvement in the progression of peritoneal fibrosis in rats with chronic renal failure.

Peritoneal fibrosis is a serious complication in patients with end stage renal disease (ESRD), especially those undergoing long-term peritoneal dialysis therapy. Since the peritoneum is a major site of mast cell accumulation, and since mast cells are known to facilitate the progression of organ fibrosis, they would also contribute to the pathogenesis of peritoneal fibrosis. The aim of this study was to reveal the involvement of mast cells in the progression of peritoneal fibrosis in chronic renal failure. Using a rat model with chronic renal failure (CRF) resulting from 5/6 nephrectomy, we examined the histopathological features of the rat peritoneum and compared them to those of age-matched sham-operated rat peritoneum. By treating the CRF rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of peritoneal fibrosis. The CRF rat peritoneum was characterized by the wide staining of collagen III and an increased number of myofibroblasts, indicating the progression of fibrosis. Compared to sham-operated rat peritoneum, the number of toluidine blue-stained mast cells was significantly higher in the fibrotic peritoneum of CRF rats. The mRNA expression of fibroblast-activating factors and stem cell factor was significantly higher in peritoneal mast cells obtained from CRF rats than in those obtained from sham-operated rats. Treatment with tranilast significantly suppressed the progression of peritoneal fibrosis in CRF rats. This study demonstrated for the first time that the number of mast cells was significantly increased in the fibrotic peritoneum of CRF rats. The proliferation of mast cells and their increased activity in the peritoneum were thought to be responsible for the progression of peritoneal fibrosis.

Mast cell-macrophage dynamics in modulation of dengue virus infection in skin.

Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient Kit(W-sh/W-sh) mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected Kit(W-sh/W-sh) mice than in DENV-infected wild-type (WT) mice (using a dose of 1 × 10(9) plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected Kit(W-sh/W-sh) mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from Kit(W-sh/W-sh) and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from Kit(W-sh/W-sh) mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated Kit(W-sh/W-sh) mice than in corresponding WT mice. In summary, compared with WT mice, Kit(W-sh/W-sh) mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.

Choroidal Mast Cells in Retinal Pathology: A Potential Target for Intervention

Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention.

The mastocyte: the off switch of UV itch.

The mastocyte: the off switch of UV itch.

The contribution of mast cells to postoperative ileus in experimental and clinical studies.

The persistent phase of postoperative ileus (POI) is mediated by inflammatory activation of the resident myeloid immune cell population in the gut wall, likely elicited by neurogenic activation. Mast cells are thought to play a critical role in this inflammatory response and involvement of mast cells in POI has been investigated and described thoroughly in experimental studies. Intestinal manipulation (IM) leads to degranulation of mast cells, resulting in an increase in mast cell proteases in peritoneal fluid and gut tissue. The inflammatory infiltrate formed in the intestinal wall thereby impairs gastrointestinal motility. In the clinical study by Berdun etal., the experimentally known association between mast cell degranulation and delayed motility is shown in a clinical setting. These findings are important and open up therapeutic opportunities to reduce or prevent POI. In this mini-review, the role of mast cells in POI is discussed. Furthermore, an update is given on the involvement of the inflammatory response in POI and potential therapeutic strategies.

Mo2034 Colonic Hypersensitivity Induced by Chronic Stress in a Stress-Sensitive Rat Strain: The Involvement of Mast Cell and Adrenergic Stimulation

Mo2034 Colonic Hypersensitivity Induced by Chronic Stress in a Stress-Sensitive Rat Strain: The Involvement of Mast Cell and Adrenergic Stimulation

Microbial Metabolite Butyrate Suppresses Murine Mast Cell Activation

BackgroundMast cell is known for its roles in mediating food allergy and regulating gut inflammation. Butyrate, a major short chain fatty acid produced by gut microbiota, exerts beneficial effects on intestinal homeostasis. However, its role in modulating mast cell function remain undefined. Methods: Murine mastocytoma P815 cells (P815) or murine bone marrow derived mast cells (BMMC) were treated with sodium butyrate (NaB). The proliferation, cell cycle, apoptosis, degranulation and cytokine secretion were assessed.ResultsIn P815 cells, NaB inhibited cell proliferation, increased acetylation of both histone 3 and α‐tubulin. The growth inhibition effect of NaB is probably through reducing c‐kit expression and inducing cell cycle arrest and apoptosis, which is indicated by enhanced annexin V/PI staining, caspase‐3 and PARP cleavage. In BMMC, NaB treatment dramatically suppressed FcεRI dependent TNFα and IL‐6 release without affecting degranulation. Furthermore, NaB enhanced histone 3 acetylation but diminished mRNA expression of Tnf ‐α and Il‐6, possibly through inhibiting the transcription initiation as revealed by reduced RNA polymerase II binding to the promoters of Tnf‐α and Il‐6.ConclusionsNaB modulates murine mast cell function possibly through enhancing histone acetylation, which is of importance in developing therapeutics for diseases involving mast cells (NIH R15HD073864).

Modulation of intestinal afferent nerve sensitivity to inflammatory mediators following systemic endotoxin in mice.

Endotoxin exposure may be followed by visceral hypersensitvity but potential mechanisms are not fully explored. We aimed to test the hypothesis that mast cells and the cyclooxygenase pathway (COX) mediate modulation of afferent nerve sensitivity following systemic endotoxin. C57Bl6 mice received endotoxin injection i.p. to induce systemic inflammation. Control animals received normal saline. Extracellular multi-unit afferent nerve discharge was recorded from jejunal mesenteric nerves in vitro. Afferent nerve response to 5-hydroxytryptamine (5-HT, 250 μmol/L), bradykinin (BK, 0.5 μmol/L), and to mechanical ramp distension of the intestinal lumen from 0 to 60 cmH2O were recorded 2 h following endotoxin administration. Following endotoxin administration peak afferent discharge to 5-HT and BK was increased compared to controls (p < 0.05). Pre-perfusion with the mast cell stabilizer Doxantrazole (10(-4) M), or the cyclooxygenase inhibitor Naproxen inhibited the increased response to 5-HT and BK (p < 0.05 vs endotoxin pretreatment). Mechanosensitivity during luminal ramp distension from 10 to 60 cmH2O was increased following endotoxin pretreatment compared to controls (p < 0.05). This increase in sensitivity following endotoxin was no longer observed after Doxantrazole or Naproxen administration for pressures from 10 to 30 cmH2O (p < 0.05). Selective COX-2 inhibition by NS398 (10 μM) but not COX-1 inhibition by SC560 (300 μM) reduced increased afferent discharge in endotoxin pretreated animals to 5-HT, BK and mechanical ramp distension from 10 to 40 cmH2O (all p < 0.05). Systemic endotoxin sensitizes mesenteric afferent nerve fibers to 5-HT, BK and mechanical stimuli. The underlying mechanism responsible for this sensitization seems to involve mast cells and the COX-2 pathway.

Fine structure and cellular responses at the host–parasite interface in a range of fish–helminth systems

A series of ultrastructural-based studies were conducted on the interface region in different fish–helminth systems: (a) an intestinal infection of the cestode Monobothrium wageneri in tench, Tinca tinca; (b) an extensive intestinal submucosa and mucosal infection in tench by metacercariae of an unidentified digenean trematode; (c) an intestinal infection in brown trout, Salmo trutta, by the acanthocephalan Dentitruncus truttae; (d) an extraintestinal infection by larvae of the acanthocephalan, Pomphorhynchus laevis in three-spined sticklebacks, Gasterosteus aculeatus; and (e) an infection in the livers of Eurasian minnow, Phoxinus phoxinus, by larvae of the nematode Raphidascaris acus. Endoparasitic helminths frequently cause inflammation of the digestive tract and associated organs, inducing the recruitment of various immune cells to the site of infection. In each of the fish–helminth systems that were studied, a massive hyperplastic granulocyte response involving mast cells (MCs) and neutrophils in close proximity to the helminths was documented. The current study presents data on the interface region in each fish–helminth system and documents the penetration of mast cells granules within the tegument of P. laevis larvae. No extracellular vesicles containing tegumental secretions from any of the four different taxa of endoparasitic helminths species at the host–parasite interface region were seen.

Targeting mast cells in gastric cancer with special reference to bone metastases.

Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumor-infiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases.

Prokinetic activity of Prunus persica (L.) Batsch flowers extract and its possible mechanism of action in rats.

The peach tree, Prunus persica (L.) Batsch, is widely cultivated in China, and its flowers have been used for centuries in traditional Chinese medicine to treat gut motility disorders. But few studies have explored the pharmacological effect of Prunus persica (L.) Batsch flowers on gastrointestinal motility. In this study, the activities of different extracts from Prunus persica (L.) Batsch flowers on the smooth muscle contractions were evaluated using isolated colon model, and the ethyl acetate extract (EAE) showed the strongest effects in vitro. EAE (10−8–10−5 g/mL) caused a concentration-dependent stimulatory effect in rat colonic tissue. Additionally, ketotifen (100 µM), cimetidine (10 µM), and pyrilamine (1 µM) produced a significant inhibition of contractions caused by EAE. Furthermore, immunofluorescence and toluidine blue staining revealed increased numbers of mast cells in the EAE group, and EAE increased histamine release from the colonic tissues. These data indicate that EAE has significant prokinetic activity and acts by a mechanism that mainly involves mast cell degranulation. Our study provides a pharmacological basis for the use of an extract of Prunus persica (L.) Batsch flowers in the treatment of gut motility disorders.

Allergen Immunotherapy Adherence in the Real World: How Bad Is It and How Can It Be Improved?

Allergen immunotherapy (AIT) is the only available causal treatment for allergic respiratory diseases; however, data demonstrate a high discontinuation rate for both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). The complex mechanism of action of allergen immunotherapy (AIT) includes an interaction of innate and adaptive immune processes, resulting in immune tolerance, as illustrated by a decrease in specific immunoglobulin (Ig)-E, an increase in specific IgG1 and IgG4, and inhibition of inflammation involving mast cells, basophils, and eosinophils. This induction of immune tolerance leads to a significant improvement in symptoms and decreased medication scores. A 3- to 5-year course of AIT is required to obtain this disease-modifying effect, which substantially differentiates AIT frompharmacologic treatment. A carry-over effect can persist for up to 12 years. Furthermore, AIT may prevent the onset of asthma in patients with allergic rhinitis, as well as decreasing the onset of new sensitizations to inhalant allergens. Several meta-analyses and controlled studies, involving adult and pediatric subjects, have indicated that both sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) are relatively safe, effective, and well tolerated. AIT may also have a positive impact on the cost to the healthcare system, as evidence indicates the cost–benefit of such treatment. Adherence to AIT is crucial for a positive clinical outcome and non-adherence represents a major drawback for such therapy. It actually concerns not only AIT but also various pharmacologic treatments for allergic respiratory diseases, as well as for other chronic illnesses. The issue of non-adherence is an emerging and worldwide problem for chronic diseases and could be an important factor responsible for an overall decrease in treatment efficacy and increased rates of hospitalization, morbidity, and mortality. This review provides an overview of the different reasons that may account for the low adherence rate for AIT. Some of these reasons can be related to the patient’s age when they begin such therapy, the allergic disease being treated, and questions about the efficacy, costs, inconvenience, and safety of AIT. Well-structured educational programs,especially by healthcare professionals, the print media, and the Internet, are needed to improve adherence to AIT.

Intraluminal Nonbacterial Intestinal Components Control Gut and Lung Injury After Trauma Hemorrhagic Shock

To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Acquired Angioedema: A Case of an Unexpected Death and Review of the Literature

Angioedema is a rapid swelling of the deep layers of skin including dermis, subcutaneous tissue, mucosa, and submucosa. It results from rapid release of inflammatory mediators that increase the permeability of capillaries and venules through mechanisms involving mast cells or bradykinin. It can be classified as allergic, drug-induced, hereditary, acquired, and idiopathic. Acquired angioedema occurs when the C1 esterase inhibitor, which plays a role in down-regulating the complement system, is absent or defective. Diagnosis of this disorder should be considered in any patient presenting with episodes of swelling affecting cutaneous tissues and mucous membranes in or beyond the fourth decade of life, without a family history of angioedema. While the disorder can occur in isolation, the majority of patients have an underlying lymphoproliferative disorder or other malignancy. The clinical course of acquired angioedema is often unpredictable and attacks can range from minor swelling to unexpected death. The following case report describes a fatality due to acquired angioedema in a man with an underlying monoclonal gammopathy of undetermined significance. A thorough review of the medical and family history, antemortem laboratory values, autopsy examination, and postmortem serum tryptase levels were all used to make the diagnosis and rule out other forms of angioedema. This case is presented, along with a review of other causes of death involving angioedema, in order to aid forensic pathologists in working up and certifying these deaths.

Impact of stress on mast cell and vitamin D receptor expression in an animal model of endometriosis (703.4)

Endometriosis is characterized by peritoneal inflammation, infertility and chronic pelvic pain that substantially affect quality of life. Since stress can affect the immune system and recruitment of inflammatory cells it may contribute to this condition. Vitamin D receptor (VDR) is associated with anti‐proliferative and anti‐inflammatory properties and is expressed in the cycling endometrium. AIM: Investigate the impact of stress on mast cells and VDR in an animal model of endometriosis. METHODS: Endometriosis was induced in female Sprague‐Dawley rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats had sutures only. Rats were exposed to either an uncontrollable or controllable stress protocol for 10 days (endo‐stress) or no stress (endo‐no stress). At sacrifice (day 60) all rats were examined for cysts. Colon and uterine tissue were analyzed for damage and myeloperoxidase (MPO) levels. Mast cell infiltration was measured by staining with toluidine blue or immunofluorescence, and VDR expression by immunohistochemistry. RESULTS: Endo‐stress rats developed more and bigger cysts than endo‐no stress rats. Uncontrollable stress resulted in higher colonic damage (p&lt;0.05) and uterine MPO compared to no stress, while controllable stress showed no difference. Uncontrollable stress increased mast cell infiltration in colonic tissue compared to controllable stress (p&lt;0.05), endo‐no stress (p&lt;0.05) and sham‐no stress (p&lt;0.01). There was increased mast cell infiltration in cysts. Endo‐no stress group had higher expression of VDR in uterus stroma nuclei and glands (p&lt;0.05 vs controllable stress; p&lt;0.05 vs sham, in glands only). CONCLUSION: Stress exacerbates development of cysts in an animal model of endometriosis through mechanisms involving mast cell recruitment, release of cell mediators and VDR down‐regulation.Grant Funding Source: Supported by R15AT006373 &amp; R25GM082406

Chemotherapy Hypersensitivity Reactions in Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer death among women in the United States. Chemotherapy using a taxane and platinum combination is key in improving survival in patients with newly diagnosed advanced ovarian cancer and is also used to treat recurrent platinum-sensitive disease. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are increasingly common and can greatly limit their use. Moreover, because of the frequent lack of equally effective alternative agents, chances of survival can be compromised. Therefore, physicians caring for these patients must be familiar with the management of HSRs to chemotherapy, and major advancements have recently been made in this field. Most HSRs implicate mast cell and basophil activation either through an IgE-mediated (ie, platinum agents) or nonspecific (ie, taxanes) mechanism. Therefore, these reactions have the potential to lead to anaphylaxis, at which time they should be treated with intramuscular epinephrine. Serum tryptase, which is released alongside histamine after mast cell activation, may be measured after an acute HSR to document mast cell involvement. After an HSR, the decision to re-treat with the same agent or a closely related one will vary depending on the causative drug, the type of HSR, and its severity. Drug desensitization has emerged as a safe and effective way of reintroducing a chemotherapeutic agent or monoclonal antibody responsible for an HSR in a patient who is expected to benefit from its continued use and for whom alternatives are considered less effective and/or more toxic. Currently, candidates for desensitization are preferably evaluated in academic settings with expertise in those procedures, because their use is still limited. Efforts are now needed to increase awareness about desensitization procedures so that more patients may benefit. This challenge will require the close collaboration of patients, nurses, oncologists, and allergists.