Exploring primary cutaneous B-cell lymphoma by microarray technology.
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Gene Expression Regulation, Neoplastic↗
Biomedical subjects
Mirjana Urosevic
Publications and source records attributed to Mirjana Urosevic.
Imiquimod induces complete clearance of a PUVA-resistant plaque in mycosis fungoides.
Imiquimod is a topical immune response modifier that binds to Toll-like receptors 7 and 8 and induces alpha-interferon. We locally applied imiquimod 5% cream (Aldara) daily for 2 weeks on a PUVA- and retinoid-resistant plaque on the face of a patient with mycosis fungoides. The diagnosis was based on clinical appearance, histology and molecular studies. Most of the disease manifestations showed a clear remission during PUVA therapy combined with low-dose retinoids. However, the plaque on the face was PUVA resistant. Local imiquimod treatment resulted in the complete clearance of the plaque. The patient has now been in complete remission for 12 months.
Adjuvants, Immunologic↗
Immunotherapy for nonmelanoma skin cancer: does it have a future?
BACKGROUND: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are the most common malignancies in the white human population, accounting for greater than 95% of nonmelanoma skin cancers (NMSCs). Current data show an increasing incidence of NMSC in recent decades. Although the mortality is low, this cancer group is associated with substantial morbidity. Multiple treatment modalities are available for NMSC, with surgery being a "cornerstone" of current therapy approaches. However, in patients with multiple lesions or in cases of tumors on critical locations, disfigurement and the disease recurrence may represent a serious problem associated with the surgical treatment. The purpose of this study was to review and analyze whether NMSC could represent a target for immune therapy, evaluating the aspects of the availability of tumor antigens and the existence of tumor specific immune response, including a summary of the major clinical studies dealing with immunotherapy for NMSC. METHODS: The authors have reviewed the available medical literature on NMSC, with a focus on tumor immunology and associated abnormalities, as well as immunotherapy-based treatment trials. RESULTS: The major advantage of NMSCs is that they arise from the skin, which makes them easily detectable and treatable. Furthermore, these tumors posses all the prerequisites, i.e., the presence of tumor-associated antigens as well as the tumor specific immune response, needed for immune intervention. This also was confirmed in various studies demonstrating clinical efficacy of cytokines and other immune response modifiers. CONCLUSIONS: In addition to clinical cure, by activating and stimulating patient's immune resources this therapeutic option may be a "silver bullet," providing a long-term protective immunity against initial tumor.
Antigens, Neoplasm↗
HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas.
Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases characterized by a clonal accumulation of lymphocytes in the skin. Most CLs display a T(h)2 cytokine profile, including expression of interleukin-10 (IL-10). Because the up-regulation of HLA-G, a nonclassical class Ib molecule inducible by IL-10, might account for the immunescape of the malignant clone, HLA-G and IL-10 expression has been investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell origin) with quantitative polymerase chain reaction (PCR) and immunohistochemistry. HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease. Except for neoplastic and infiltrating lymphocytes, other cells such as macrophages and dendritic cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which correlated with HLA-G protein presence (P <.001). HLA-G up-regulation together with IL-10 expression in CL might additionally contribute to the evasion of immunosurveillance and facilitate the transition from low- to high-grade lymphomas.
Adolescent↗
HLA-G and its KIR ligands in cancer--another enigma yet to be solved?
Alterations of antigen-presenting human leukocyte antigen (HLA) molecules often occur in cancer and represent one of the mechanisms by which tumours evade host immunosurveillance. One such molecule, HLA-G, was recently implicated in the same context. HLA-G is thought to mediate the tolerance of the semi-allogeneic fetus during pregnancy, by inhibiting maternal immune response through interaction with different HLA-G-recognizing killer-cell inhibitory receptors (KIRs). A report in this issue of the journal demonstrates for the first time the expression of HLA-G and its KIR ligand, ILT-2 in human breast cancer. Apart from the up-regulation on tumour cells, the authors describe HLA-G induction on the macrophages and T cells infiltrating the breast cancer lesions. Moreover, a subset of infiltrating cells also expressed HLA-G-recognizing KIR, ILT-2. This editorial discusses the induction of HLA-G and related KIR molecules as another mechanism for tumours to escape immune recognition.
Breast Neoplasms↗
Real-time polymerase chain reaction monitoring of epithelial cell adhesion molecule-induced T-cell stimulation in patients with lung cancer and healthy individuals using LightCycler technology.
The epithelial cell adhesion molecule is strongly expressed in carcinomas of diverse histologic origin and has attracted attention as a target for immunotherapy. We have previously demonstrated that the epithelial cell adhesion molecule-derived human leukocyte antigen-A*0201-restricted nonamer peptide ILYENNVIT(184-192) can be efficiently recognized by peptide-specific cytotoxic T lymphocytes (CTL). Using this peptide (Ep-2) we could readily expand precursor CTL and demonstrate their cytotoxicity by standard chromium-release assay. We now sought to evaluate the immune reactivity of Ep-2-specific CTL expanded from the peripheral blood mononuclear cells by real-time quantitative polymerase chain reaction assay (LightCycler system) measuring the change in interferon-gamma mRNA levels upon stimulation. Cytotoxic T lymphocyte response against the Ep-2 peptide in two patients with epithelial cell adhesion molecule-expressing lung cancer and three healthy donors was compared with the chromium-release assay. In vitro expanded epithelial cell adhesion molecule-specific CTL precursors that exhibited significantly elevated interferon-gamma mRNA levels also lysed Ep-2 peptide-pulsed target cells. Our study indicates that quantitative polymerase chain reaction may be a supplement to chromium-release assay for monitoring in vitro expanded CTL precursor reactivity.
Antigens, Neoplasm↗
Immune reactivity against a novel HLA-A3-restricted influenza virus peptide identified by predictive algorithms and interferon-gamma quantitative PCR.
The use of appropriate antigenic peptides for the most common human major histocompatibility complex (MHC) alleles is required for the amplification of the autologous cytotoxic compartment and the development of cytotoxic T cell-mediated immunity. The human A2 allele of the MHC plays an important role for the identification of peptide-specific cytotoxic T cells (CTL) against tumor and viral epitopes. Computer-based prediction algorithms, which are available on the Internet, have already proved to be applicable for the identification of novel CTL epitopes. Using the bioinformatics approach, the authors have identified the novel influenza matrix protein-derived and HLA-A3-restricted 9-mer peptide RLEDVFAGK capable of inducing peptide specific CTL reactivity. Peripheral blood mononuclear cells (PBMC) from healthy individuals and patients with lung cancer were pulsed with this peptide and with the well-characterized HLA-A2-restricted influenza A virus matrix peptide GILGFVFTL. Using quantitative PCR (TaqMan; Applied Biosystems, Foster City, CA, U.S.A), reactivity for both peptides was determined by measuring the change in type 1 cytokine (IFN-gamma) expression upon in vitro stimulation. Peptide-specific reactivity matched well with the subsequently determined MHC-class I alleles of the tested individuals. Results from this study indicate that the use of bioinformatics and the PCR-based screening system for the monitoring of T cell reactivity may allow for the identification of novel CTL epitopes.
Algorithms↗