Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function.

The in-depth understanding of skin resident memory CD8+ T lymphocytes (TRM ) may help to uncover strategies for their manipulation during disease. We investigated isolated TRM from healthy human skin, which expressed the residence marker CD69, and compared them to circulating CD8+ T cell populations from the same donors. There were significantly increased proportions of CD8+ CD45RA- CD27- T cells in the skin that expressed low levels of killer cell lectin-like receptor G1 (KLRG1), CD57, perforin and granzyme B. The CD8+ TRM in skin were therefore phenotypically distinct from circulating CD8+ CD45RA- CD27- T cells that expressed high levels of all these molecules. Nevertheless, the activation of CD8+ TRM with T cell receptor (TCR)/CD28 or interleukin (IL)-2 or IL-15 in vitro induced the expression of granzyme B. Blocking signalling through the inhibitory receptor programmed cell death 1 (PD)-1 further boosted granzyme B expression. A unique feature of some CD8+ TRM cells was their ability to secrete high levels of tumour necrosis factor (TNF)-α and IL-2, a cytokine combination that was not seen frequently in circulating CD8+ T cells. The cutaneous CD8+ TRM are therefore diverse, and appear to be phenotypically and functionally distinct from circulating cells. Indeed, the surface receptors used to distinguish differentiation stages of blood T cells cannot be applied to T cells in the skin. Furthermore, the function of cutaneous TRM appears to be stringently controlled by environmental signals in situ.

An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

BACKGROUND: Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirror that of humans. METHODS: We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of antitumour IgE antibodies. RESULTS: In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a "cytokine storm" or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated antitumour and antiparasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. CONCLUSION: Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena.

Clinical relevance of immunogenicity of biologics in psoriasis: implications for treatment strategies.

Biological drugs such as the tumour necrosis factor inhibitors have revolutionized the treatment of psoriasis, but some have the potential to induce an unwanted immune response. This immunogenicity may be associated with low trough drug levels, reduced clinical efficacy, reduced drug survival and an increased risk for adverse events. This article presents a literature review of the evidence on immunogenicity of biologics used in the treatment of psoriasis and considers the implications for therapeutic decision-making in the management of patients with moderate-to-severe psoriasis.

Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE: To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS: A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS: The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION: This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

The mechanistic basis for psoriasis immunopathogenesis: translating genotype to phenotype. Report of a workshop, Venice, 2012.

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the pathogenic mechanisms that constitute psoriasis. In September 2012, a workshop was held at the 42nd Annual European Society for Dermatological Research in Venice, Italy. By assembling a panel of global dermatology and immunology experts, the objective was to evaluate the current status of the science explaining the mechanism of disease in psoriasis, e.g. dysregulation of the skin immune system and perturbations of epidermal homeostasis. The workshop consisted of four oral presentations, which addressed key topics in psoriasis, delivered by Hervé Bachelez (Paris, France), Antonio Costanzo (Rome, Italy), Michelle Lowes (New York, NY, U.S.A.) and Frank Nestle (London, U.K.). A global expert panel was assembled to stimulate dialogue and debate: Kevin Cooper (Cleveland, OH, U.S.A.), Michel Gilliet (Lausanne, Switzerland), Joerg Prinz (Munich, Germany), Martin Röcken (Tubingen, Germany), Jens Schroeder (Kiel, Germany), Manuelle Viguier (Paris, France), Mayte Suárez-Fariñas (New York, NY, U.S.A.) and Cristina Zielinski (Berlin, Germany). Collectively, the presentations demonstrated the significant advances in understanding immune regulation that have occurred over the past decade by virtue of the study of psoriasis subtypes, phenotypic manifestations and genetic associations. Elucidating the pathogenic and genetic basis of psoriasis holds the promise of a complete understanding of disease mechanisms, predictors of treatment response, novel drug development strategies and customized therapeutic regimens for the individual patient.

Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcɛRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity.

BACKGROUND: IgE antibodies, sequestered into tissues and retained locally by the high-affinity IgE receptor, FcɛRI, on powerful effector cells such as mast cells, macrophages and eosinophils, may offer improvements in the therapy of solid tumours. The chimeric antibody, MOv18 IgE, against the human ovarian carcinoma antigen, folate receptor α (FRα), is more effective than its IgG1 counterpart in xenograft models of ovarian cancer. Although MOv18 IgE binds to a single epitope on FRα and cannot cross-link IgE receptors on basophils, there remains a risk that components in the circulation of ovarian cancer patients might cross-link FRα-MOv18-IgE-receptor-FcɛRI complexes on basophils to cause type I hypersensitivity. OBJECTIVE: To assess the propensity for MOv18 used in a therapeutic setting to cause FcɛRI-mediated type I hypersensitivity. METHODS: As validated readouts of the potential for MOv18 to cause FcɛRI-mediated type I hypersensitivity we measured release of a granule-stored mediator from a rat basophilic leukaemia cell line RBL SX-38 stably transfected with human tetrameric (αßγ2) FcɛRI, and induction of CD63 on blood basophils from patients with ovarian carcinoma and healthy controls ex vivo. RESULTS: Serum FRα levels were increased in ovarian cancer patients compared with healthy controls. MOv18 IgE alone, or in the presence of its antigen recombinant human FRα, or of healthy volunteer (n=14) or ovarian carcinoma patient (n=32) sera, did not induce RBL SX-38 cell degranulation. Exposure to FRα-expressing ovarian tumour cells at target-to-effector ratios expected within tumours induced degranulation. MOv18 IgE did not induce expression of CD63 in blood basophils from either healthy volunteers (n=6), or cancer patients, despite detectable levels of circulating FRα (n=5). CONCLUSION AND CLINICAL RELEVANCE: These encouraging data are compatible with the hypothesis that, when ovarian carcinoma patients are treated with MOv18, FcɛRI-mediated activation of effector cells occurs within the tumour mass but not in the circulation mandating, with due caution, further pre-clinical studies.

Dendritic cells: On the move from bench to bedside.

As dendritic cells increasingly become the adjuvant of choice in new approaches to cancer immunotherapy, a degree of protocol standardization is required to aid future large-scale clinical trials.

Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.

Melanoma is the main cause of death in patients with skin cancer. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified. These antigens are suitable candidates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a primary T-cell response. Mouse studies have demonstrated the potent capacity of DCs to induce antitumor immunity. In the present clinical pilot study, DCs were generated in the presence of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) and were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunological tracer molecule. Sixteen patients with advanced melanoma were immunized on an outpatient basis. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of the patients. DC vaccination induced delayed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pulsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the DTH challenge site was also demonstrated. Therefore, antigen-specific immunity was induced during DC vaccination. Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response. These data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of melanoma patients.

Regression of melanoma metastases following treatment with the n-bisphosphonate zoledronate and localised radiotherapy.

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

Local activation of T lymphocytes is regarded as an important immunological component of psoriatic skin lesions. Within psoriatic plaques (PP) there are large numbers of dermal dendritic cells (DDCs) immediately beneath the hyperplastic epidermis surrounded by T cells. In this study we investigated the ability of DDCs isolated from PP skin to support immune responses to resting peripheral blood T cells. For comparison, other dendritic cells were obtained from blood of the same psoriatic patients, as well as DDCs from skin of normal healthy individuals (designated NN skin). All dendritic cells studied had high surface expression of HLA-DR, B7, and lymphocyte function associated antigen-1 molecules. T cell proliferative responses and cytokine production profiles to these various dendritic cells were measured in the absence and presence of PHA or bacterial-derived superantigens. In the absence of exogenous mitogens, PP skin-derived DDCs were much more effective stimulators of spontaneous T cell proliferation compared with either psoriatic blood-derived or NN skin-derived dendritic cells. Antibody blocking studies revealed involvement of HLA-DR, B7, and lymphocyte function associated antigen-1 on PP skin-derived DDCs. Cytokine profiles revealed that in the absence of exogenous stimuli PP skin-derived DDCs mediated a T cell response with high levels of IL-2 and IFN-gamma, but not IL-4 or IL-10. NN skin-derived DDCs produced a similar qualitative response, but quantitative amounts of all cytokines measured were lower. Upon addition of PHA or superantigens, both PP skin-derived and NN skin-derived DDCs mediated high levels of IL-2 and IFN-gamma production, with induction of IL-4 particularly evident for PHA reactions. Addition of conditioned medium from psoriatic dermal fragments did not enhance the autostimulatory capacity of blood-derived dendritic cells. These findings highlight the potent autostimulatory potential of PP skin-derived DDCs and suggest an important immunological contribution for these previously overlooked cell types contained within lesional skin sites.

Dendritic cell vaccination for cancer therapy.

A growing list of defined tumor-antigens opens the way to antigen specific immunotherapy of cancer. However current approaches are often limited in their potential to induce an effective anti-tumor response. Dendritic cells (DC) are natural adjuvants for the induction of antigen specific T cell response. They have been successfully used in clinical pilot trials to induce tumor specific immunity as well as clinical response in selected patients. Current research focuses on optimization of DC source, choice of antigen, antigen loading, mode of injection, as well as immuno-monitoring. Finally, a variety of immune escape mechanisms are operative at the tumor site and have to be overcome for successful vaccination.

Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper.

Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.

Human dermal dendritic cells process and present soluble protein antigens.

Recently, a novel type of dendritic antigen-presenting cell has been identified in the dermis of normal human and mouse skin. These dermal dendritic cells (DDC) occur in higher numbers than epidermal Langerhans cells, represent a distinct differentiation pathway of dendritic cells, and are as potent as Langerhans cells in the activation of superantigen specific T cells. As yet, nothing is known about their capacity to take up, process, and present soluble protein antigens. We used the model of tetanus toxoid (TT) driven T cell proliferation to address these questions. To test for active internalization of TT protein, gold labeled TT was incubated with Langerhans cells and DDC and could be traced to multivesicular endo-lysosomal compartments. DDC internalize TT through a receptor-mediated, clathrin-independent pathway, whereas Langerhans cells predominantly use macropinocytosis. To verify that DDC process TT by the exogenous pathway of antigen presentation, we pulsed DDC with TT protein or TT peptide after preincubation with chloroquine. Preincubation with chloroquine diminished the capacity of DDC to induce TT protein specific T cell proliferation (70-80%), but was not effective to suppress TT peptide induced T cell responses. DDC were as potent as Langerhans cells and 5-10 x more potent than plastic adherent monocytes in the presentation of TT to autologous resting T cells. Furthermore, as few as 50 DDC (stimulator:responder ratio of 1:1000) were able to induce a significant TT specific T cell proliferation. Because a subpopulation of DDC expresses low levels of CD1a, a phenotypic marker of Langerhans cells, sorting of CD1a positive and negative DDC was performed. On a per cell basis, CD1a positive and negative DDC were equally potent at mediating TT specific T cell proliferation. Thus, DDC are able to internalize, process, and present soluble protein antigens such as TT and may therefore play an important role in the regulation of skin immune responses.

Cationic lipid is not required for uptake and selective inhibitory activity of ICAM-1 phosphorothioate antisense oligonucleotides in keratinocytes.

Keratinocyte intercellular adhesion molecule-1 (ICAM-1) is important in mediating retention of T cells within the epidermal compartment. To determine if antisense oligonucleotides designed to hybridize to various ICAM-1 mRNA regions could selectively influence cultured keratinocyte ICAM-1 expression following gamma interferon (IFN-gamma), cells were exposed to several antisense compounds, in the absence and presence of cationic lipid (lipofectin). Keratinocytes rapidly internalized sense and antisense compounds (within 30-60 min), even in the absence of lipofectin with approximately 30% of the cell possessing positive nuclei. Such nuclear accumulation was not observed in the absence of lipofectin in cultured fibroblasts, smooth muscle cells, or endothelial cells, even though total cellular uptake within the cytoplasm was significantly increased in all these cell types. Using flow cytometry, IFN-gamma-inducible ICAM-1 expression was reduced 50% by antisense compounds with lipofectin, and by 30% without lipofectin. This inhibition was specific as no change was observed for HLA-DR or tumor necrosis factor-alpha receptor expression. Northern blot hybridization studies confirmed that ICAM-1 antisense oligonucleotides selectively and significantly inhibited ICAM-1 expression. These results suggest that such antisense compounds interact with keratinocytes differently than other cell types, and provide the in vitro basis for clinical trials in which reduction (or elimination) of ICAM-1 expression by epidermal keratinocytes could be selectively accomplished without necessarily influencing dermal cell types such as fibroblasts, endothelial cells, or smooth muscle cells.

Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells.

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.

Direct and indirect control of T-cell activation by keratinocytes.

Keratinocytes can function as antigen-presenting cells/accessory cells and regulate T cells with three distinct outcomes, depending on the nature of the stimulus. In the presence of alloantigen, it appears that a "null" event takes place between T cells and keratinocytes, with neither activation nor induction of tolerance. Using nominal antigen, keratinocytes induce antigen-specific tolerance. In contrast, with bacterial-derived superantigens, phytohemagglutinin, or immobilized CD3 monoclonal antibody, keratinocytes can significantly activate resting autologous T-cell proliferation and cytokine release. To understand these highly divergent responses, we focused on the two-signal model of T-cell activation, with particular emphasis on costimulatory molecules expressed by keratinocytes. Such second signals, as highlighted by the B7 and CD28 receptor families, provide useful insights into the complex interactions involving keratinocytes and T cells. In this review, we summarize recent evidence indicating that keratinocytes regulate T-cell activation in a direct and indirect manner by their mutual expression and responsiveness involving adhesion molecules, cytokines, and costimulatory signals. As investigative momentum continues to grow in the fields of immunology and keratinocyte biology, it is likely that manipulation of CD28:B7 interactions will not only provide a useful model to understand further the complexities of skin immune reactions, but will also serve as the basis for new therapeutic opportunities for numerous T-cell-mediated diseases that involve aberrant reactions with keratinocytes.

Extracorporeal photochemotherapy for Epstein-Barr virus-associated lymphoma after lung transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication after transplantation of solid organs. Highest incidence rates have been reported for lung transplant recipients. With the current treatment strategy for early onset PTLD, a reduction of immunosuppressive drugs, mortality of lung transplant recipients with PTLD remains high, due to both, incomplete control of PTLD and transplant rejection. We present a lung transplant recipient with a history of acute rejection and Epstein Barr virus-associated posttransplantation malignant non-Hodgkin's lymphoma. Extracorporeal photochemotherapy, in combination with a moderate reduction of immunosuppressive therapy, resulted in complete disappearance of PTLD. After a first year of follow-up, no further rejection and no recurrence of PTLD have occurred. Treatment with ECP, with its beneficial effects on both, rejection after organ transplantation and malignant lymphoma, may be a particularly valuable approach for the treatment of PTLD in patients after lung transplantation, with its increased risk for transplant rejection.

Melanoma vaccines in development: looking to the future.

There is a body of evidence indicating that melanoma is an antigenic tumour. Since the efficacy of standard therapy in advanced stages of melanoma is rather poor, experimental immunotherapy aims to target this aggressive neoplasm. After the identification of several melanoma antigens, vaccination trials have been initiated in patients with metastatic disease using peptides, dendritic cells and gene therapy approaches including viral vectors or naked DNA. If the problems in inducing a constant and potent T cell response are solved, the stability of melanoma antigens and their presentation will decide whether these treatment approaches will reach significant relevance in daily clinical practice.

Pityriasis rosea is not associated with human herpesvirus 7.

OBJECTIVE: To examine the proposed association between pityriasis rosea and human herpesvirus 7 (HHV-7). DESIGN: A retrospective cross-sectional survey. SETTING: University medical center in Switzerland. PATIENTS: Thirteen patients with pityriasis rosea and 14 persons with normal skin (control subjects). MAIN OUTCOME MEASURES: Detection of HHV-7-specific DNA sequences and antigen (85-kd phosphoprotein [pp85]) by nested polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Human herpesvirus 7 DNA sequences and expression of the HHV-7-specific immunodominant pp85 antigen were found in 1 (8%) of 13 lesional skin biopsy specimens of pityriasis rosea. The prevalence of HHV-7 DNA sequences and antigens is even slightly lower in lesional skin of patients with pityriasis rosea than in clinically and morphologically normal skin of 14 control persons, in 2 of whom (14%) HHV-7 DNA sequences and antigens could be detected. CONCLUSION: The low detection rate of HHV-7 DNA sequences and antigens argues strongly against a causative role for HHV-7 in the pathogenesis of pityriasis rosea.

Autologous dendritic cells for treatment of advanced cancer--an update.

Dendritic cells (DC) are commonly viewed as the professional antigen-presenting cell. They capture antigens, migrate to appropriate lymphoid organs and initiate an antigen-specific CD4 and CD8 T cell response. Much is known about DC physiology, and it is now possible to culture, maintain and expand DC from different human sources, including hematopoietic progenitors in bone marrow and peripheral blood. Combined with the detection of an increasing number of tumor-associated antigens and T cell-recognized peptide epitopes, this has led to a new enthusiasm in the field of tumor immunotherapy and to various clinical applications in phase I/II studies on the treatment of different malignancies. This chapter will review the latest developments and give a brief update of the results obtained in studies of advanced melanoma, as well as provide a short overview of published results for other tumors.