Search results for "chemical and pharmacologic phenomena"
showing 10 items of 616 documents
Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML…
2008
Objective Current in vitro techniques for isolating leukemia-reactive cytotoxic T lymphocytes (CTLs) from healthy donors are of relatively low efficiency and yield responder populations with unknown biological significance. This study aimed at the development of a more reliable approach, allowing generation and expansion of acute myeloid leukemia (AML)-reactive CTLs using primary in vitro stimulation. Materials and Methods We established allogeneic mini-mixed lymphocyte-leukemia cultures (mini-MLLCs) by stimulating donor CD8 + T cells with human leukocyte antigen (HLA) class I–matched AML blasts in microtiter plates. Before culture, CD8 + T cells were separated into CD62L (high)+ and CD62L …
Investigation of the immune infiltrate of melanoma metastases under immune checkpoint inhibition.
2017
9570 Background: Tumor infiltrating lymphocytes (TIL) play a crucial role in the therapeutic impact of immune checkpoint blockers. Methods: We investigated metastases from 56 melanoma patients before and during treatment with immune checkpoint blockers (i) immunohistochemically, (ii) with TCR repertoire profiling and (iii) analysis of the transcriptome. The patients were treated with ipilimumab (n = 25) or pembrolizumab (n = 23) or ipilimumab/nivolumab (n = 7); half of them had a disease control, the other half progressed as best response to treatment. Results: In contrast to previous reports immunohistochemical analysis of the immune infiltrate revealed no significant difference in the nu…
The effect of Keyhole Limpet Hemocyanin (KLH) on the rat bladder
1977
Immunostimulation with agents such as BCG or KLH may represent an adjuvant therapy in treating patients with bladder cancer. To investigate the effects of direct instillation and injection of KLH into the bladder of sensitized and nonsensitized rats, KLH was injected submucosally into the bladder. Histologically, a marked inflammatory reaction was seen without ulcerations.
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
2006
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
The number of intratumoral dendritic cells and ?-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma
2001
BACKGROUND Dendritic cells (DCs) are antigen-presenting cells with a unique ability to cross prime T cells and generate strong antitumor responses. This study evaluates the presence and prognostic significance of DCs as well as functional T cells, which accumulate in the microenvironment in patients with oral squamous cell carcinoma (OSCC). METHODS Immunohistochemistry for S-100 positive or p55 positive DCs and for T-cell receptor (TcR)-associated ζ-chain expression in tumor-infiltrating lymphocytes (TILs) was performed in 132 paraffin embedded specimens from patients with primary OSCC. The median clinical follow-up for the patients was 50 months. The numbers of intratumoral DCs or TILs exp…
Analysis of the prognostic impact of Treg-related genes in tumor and stroma in resectable NSCLC
2013
11073 Background: Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed the expression of 11 genes related to Tregs in both tumor and stroma samples of resectable NSCLC patients. Methods: Primary tumor tissues of FFPE samples from 125 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a …
Human FOXP3 and cancer.
2010
FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…
Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?
2002
alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant V alpha 14 J alpha 281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. …
Partial tyrosinase-specific self tolerance by HLA-A*0201-restricted cytotoxic T lymphocytes in mice and man
2003
The human tyrosinase (hTyr) (369-377) cytotoxic T lymphocyte (CTL) epitope is presented by malignant melanoma and various nontransformed cells in association with human leukocyte antigen (HLA)-A*0201 (A2.1) and used for vaccination-based immunotherapy of melanoma patients. Its mouse homologue, mTyr (369-377), is naturally processed and bound by A2.1 with equivalent efficacy and thus enabled us to explore the effect of self tolerance on Tyr-specific T cells in different lines of A2.1 transgenic (Tg) mice and man. We found that self Tyr-reactive CTL in Tg mice and, importantly, in man were affected by partial tolerance resulting in only residual T lymphocytes of higher avidity for self Tyr al…
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
2021
Abstract Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intravent…