Search results for " lymphocyte"
showing 10 items of 437 documents
Genetic evolution of T-cell resistance in the course of melanoma progression
2014
Abstract Purpose: CD8+ T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. Experimental Design: One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell–stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alteratio…
Induction of tumor-cell lysis by bi-specific antibody recognizing ganglioside GD2 and T-cell antigen CD3
1993
Human tumor cells expressing ganglioside GD2 were lysed by various effector populations targeted with an anti-CD3-anti-GD2 bi-specific antibody (BAb CD3 x GD2). This antibody-heteroconjugate was prepared by chemically cross-linking the OKT-3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes with the ganglioside MAb ME 361, which binds preferentially to the tumor-associated ganglioside GD2. The specificity of target-cell lysis by the cytotoxic T cells (CTL) was mediated by the specificity of the targeting antibody: GD2-negative cells were not lysed in the presence of the CD3 x GD2 BAb. A dose-dependent response was observed in a range of 10 to 10,000 ng/ml. In contrast, 2 …
Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic t lymphocytes (CTL)
1993
We have pursued our analysis of potential tumor-rejection antigens recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29-MEL in association with HLA-A2. Selection for melanoma-cell variants resistant to anti-A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor-cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA-B45, indicating that this CTL may also recognize a determinant of an…
Overlapping peptides of melanocyte differentiation antigen melan-A/MART-1 recognized by autologous cytolytic T lymphocytes in association with HLA-B4…
1998
From the peripheral blood lymphocytes (PBLs) of melanoma patient SK29(AV) we have previously isolated 2 independent cytolytic T lymphocyte (CTL) clones (CTL7/147 and CTL13/211), which lysed autologous tumor cells in association with HLA-B45.1. As demonstrated here, both CTL clones were directed against melanocyte differentiation antigen Melan-A/MART-1, which also was recognized by HLA-A2.1-restricted CTLs from the same patient. By generating and transfecting 3'-deletion mutants of Melan-A/MART-1 cDNA, we localized its peptide-coding regions. The HLA-B45.1-presented peptides were derived from a hydrophobic region of the protein and largely overlapped the peptides recognized by CTLs from the …
Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic proge…
2001
Stromal cell-derived factor-1alpha (SDF-1alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1. It is required during hematopoiesis and homing of HPC to the BM. As HPC migration in response to SDF-1alpha might require dynamic regulation of integrin function, we investigated if SDF-1alpha could modulate VLA-4 function on BM CD34(hi) cells.CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1alpha on VLA-4-dependent adhesion to CS-1/fibr…
Cellular immune response to human renal-cell carcinomas: Definition of a common antigen recognized by HLA-A2-restricted cytotoxic T-Lymphocyte (CTL) …
1994
Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross-reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2-pos…
Blood T-cell Vβ transcriptome in melanoma patients
2004
Tumor-cells have been shown to elicit MHC-restricted and antigen-specific T-cell responses. In this article, we used a new approach to study T-cell responses in tumor-bearing patients based on a global representation of the Vβ-transcriptome, making it possible to grade CDR3-length distribution (CDR3-LD) alterations. Six patients with advanced melanoma disease, from whom blood samples were taken before and serially after tyrosinase-A peptide vaccination, were studied. The PBMC from patients displayed highly significant Vβ transcriptome alterations as compared to healthy individuals. Similar Vβ alterations could be detected both in PBMCs and at the tumor site. After vaccination, Vβ alteration…
Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?
2019
e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasm…
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…
Enhanced expression of ELAM-1 on endothelium of renal cell carcinoma compared to the corresponding normal renal tissue
1999
Abstract Renal cell carcinoma (RCC) has been shown to respond to an immunological therapy with tumor infiltrating lymphocytes (TIL), which accumulate in RCC at a higher density than in normal renal tissue, suggesting that there is selective tumor invasion. Since invasion of TIL into the malignant tissue is mediated by adhesion molecules, we examined the different expression of the adhesion molecule endothelial-leukocyte-adhesion-molecule-1 (ELAM-1) on endothelial cells of RCC versus normal renal tissue. For a specific quantification, the level of ELAM-1 mRNA was investigated by both semi-quantitative reverse transcription–polymerase chain reaction (RT–PCR) and Northern blot analysis and ref…