Search results for "Immune system"

Oncolytic parvovirus H1 induces release of heat-shock protein HSP72 in susceptible human tumor cells but may not affect primary immune cells.

2003

Certain autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and may reduce the incidence of spontaneous and implanted tumors in animals. Hence, these viruses and their derivatives are currently under evaluation as antitumor vectors. However, the mechanisms underlying their tumor-suppressing properties are not yet understood. We asked whether the lytic parvovirus H1 may enhance the immunogenicity of infected tumor cells. Out of human melanoma and gastrointestinal tumor cells, we selected the cell line SK29-Mel-1 being very susceptible to H1-induced apoptotic killing. Here, no upregulation of HLA class I and costimulatory molecules could be observed followi…

Lactate: A Metabolic Key Player in Cancer

2011

Abstract Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate…

Abstract 1847: Anti-GARP antibody DS-1055a augments antitumor immunity by depleting highly suppressive GARP+ regulatory T cells

2021

Abstract Immune checkpoint blockers (ICBs) have drastically changed the clinical care of cancer; however, the population of patients who can benefit is relatively small because of intrinsic or acquired resistance to immune therapy. To evade immune destruction, tumors exploit several distinct strategies including immunosuppressive cells such as regulatory T (Treg) cells. Treg cells, an essential component for maintaining self-tolerance, inhibit antitumor immunity, consequently hindering protective cancer immunosurveillance and hampering effective antitumor immune responses in tumor-bearing hosts. It is often reported that a high ratio of Treg cells to effector CD8+ T cells is associated with…

2004

Tumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A-specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A-specific CTLs revealed a high cytolytic activity against allogeneic Melan-A-expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of the codin…

2004

Address: 1I. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany, 2Deutsches Krebsforschungszentrum, Applied Tumor Virology, Dept. F0100, and Institut National de la Sante et de la Recherche Medicale Unite 375, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany, 3III. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany and 4Med. Department Mitte, Klinikum Dortmund GmbH, Beurhausstr. 10, 44137 Dortmund, Germany

Abstract 4740: Doxorubicin eliminates tumor-induced myeloid-derived suppressor cells and enhances T-helper lymphocyte-based immunotherapy in a murine…

2013

Abstract Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of cells equipped with the ability to inhibit T lymphocyte-mediated immune responses. A significant increase in the number of MDSC has been reported in the blood, secondary lymphoid organs and tumor beds in tumor-bearing animals and in patients with many types of cancers. MDSC frequency correlates with the disease stage and prognosis. These cells impair CD8+ cytotoxic T lymphocyte (CTL)-mediated anti-tumor immunity by different overlapping mechanisms such as reactive oxygen species or immunosuppressive cytokine production. Importantly, MDSC elimination or inactivation substantially enhances the efficiency …

Humoral immune responses of cancer patients against “Cancer-Testis” antigen NY-ESO-1: Correlation with clinical events

1999

Humoral immune responses against the "Cancer-Testis" (CT) antigen NY-ESO-1 are frequently observed in patients with NY-ESO-1 expressing tumors. This is in contrast to other known tumor antigens (TA) defined by antibody or cytotoxic T cell (CTL) reactivity, i.e., MAGE-1, MAGE-3, SSX2, Melan A, and tyrosinase. No NY-ESO-1 antibody has been detected in healthy controls and patients with NY-ESO-1 negative tumors. In this study, we have assessed the NY-ESO-1 serum antibody response in patients with NY-ESO-1 positive tumors of different histological types and stages using Western blotting and an ELISA. Of the 12 patients analyzed, 10 had demonstrable NY-ESO-1 antibodies at the start of the study.…

2004

RHAMM/CD168 was defined as a LAA using the approach of serological screening of expression libraries (SEREX), eliciting IgG responses in 42% of patients with AML, but not in healthy volunteers (HV) or patients with autoimmune diseases. mRNA for RHAMM was demonstrated by qRT-PCR to be expressed in leukemic blasts of more than 80% of the AML patients, but not in PBMN or CD34+ stem cells of healthy volunteers. Among normal tissues, only testis, placenta and thymus showed significant mRNA expression for the antigen, therefore sharing the expression profile of some other SEREX antigens.

A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.

2019

e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their poten…

Exome Sequencing to Predict Neoantigens in Melanoma

2015

Abstract The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to u…