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Bernard Bonnotte

Publications and source records attributed to Bernard Bonnotte.

11 recordsLinked to original sources
PubMed2006

Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loading.

The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs. However the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial. In this study we have induced and defined 3 distinct mechanisms of tumor cell death (apoptosis, necrosis and fusion-mediated cell death), and investigated their differential effects on DCs. Bone marrow-derived DCs demonstrated comparable uptake of primary apoptotic, necrotic, or fused dead tumor cells. Furthermore, the distinct modes of cancer cell death had analogous potential in activating the transcription factors NF-kappaB and STAT1 and in maturing DCs, resulting in an equally effective stimulation of immune T cells. The current study therefore provides further informations on the use of dead whole tumor cells as antigen sources for effective active anti-cancer immunotherapy.

Animals↗
PubMed2004

[The interest of a short-lived orientation unit in a department of internal medicine].

OBJECTIVE: To assess the activity of a short-lived orientation unit (SLO) with 9 beds that only receives patients from the emergency department in whom diagnosis and/or specific treatment must be set-up while awaiting a vacant bed in the appropriate medical department. METHODS: During the 29 months after the creation of the SLO (Feb. 2001 to June 2003), we analysed the parameters supplied every month by the medical computer department: number of patients hospitalized in the SLO, age, gender, principle diagnosis according to the PMSI coded data, duration of hospitalisation, number of deaths, number of releases direct to home, number of transfers to a specialized unit and qualification of the referral units. RESULTS: 1840 patients (mean age: 73 years) were hospitalized in this unit. The most frequent diseases were bronchopneumonia (16%), syncope episode (14%), cerebral stroke (12%), thromboembolic diseases (11%) and heart failure (10%). The mean duration of hospitalization was 3.7 days (less than 48 hours in 46% of cases). In 40% of cases, patients were able to return directly to their homes. In 62% of cases, the patients were referred to a specialised unit within 48 hours. The functioning of the SLO has various specificities (repeated personalised telephone contacts, letters for rapid transfer, difficult co-operation with certain departments...). CONCLUSION: The SLO is useful for patients since it accelerates their adapted management and allows quick transfer to the unit adapted to their pathology, permitting correct adequation between the pathologies of the patients and the competence of the specialised medical unit.

Aged↗
PubMed2004

MIP-3alpha transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity.

Dendritic cells are powerful APCs for activation of specific antitumor T lymphocytes. To present tumor Ags efficiently, they have first to migrate to the tumor site, engulf Ag, and then process them. To attract immature DCs to the tumor site, we transfected tumor cells with MIP-3alpha which is strongly chemotactic for DCs. Surprisingly, MIP-3alpha-transfected tumor cells grew faster than the mock-transfected tumor cells. Histological analysis and tumor dissociation confirmed that the MIP-3alpha-transfected tumors contain three to four times more DCs than mock-transfected tumors. FACS analysis of the intratumor DCs showed that they were predominantly immature. Functional analysis showed that the alloreactivity mediated by these infiltrating MIP-3alpha-transfected tumor DCs is strongly reduced. In conclusion, MIP-3alpha is an efficient chemokine for attracting DCs in vivo, but the high density of DCs in the tumor site injection is not a sufficient condition to induce an immune response. Furthermore, this attraction of immature DCs may always have an adverse effect by inducing a tolerance to the tumor cells.

Animals↗
PubMed2004

CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative.

We investigated the mechanisms of immune tolerance raised by tumors by comparing immunogenic and tolerogenic tumor cell clones isolated from a rat colon carcinoma. When injected into syngeneichosts, the immunogenic REGb cells yield tumors that are rejected, while the tolerogenic PROb cells yield progressive tumors and inhibit the regression of REGb tumors. We show here that PROb tumor volume is correlated with an expansion of CD4(+)CD25(+) regulatory T lymphocytes in lymphoid tissues. These cells delay in vivo the rejection of REGb tumors and inhibit in vitro T cell-mediated immune responses against REGb cells through a mechanism that requires cell contact between effector and regulatory T cells and involves TGF-beta. While total T cells fromPROb tumor-bearing rats yield no apparent anti-tumor immune response, depletion of CD25(+) T cells restores this reactivity. A single administration of cyclophosphamide depletes CD4(+)CD25(+) T cells in PROb tumor-bearing animals, delays the growth of PROb tumors, and cures rats bearing established PROb tumors when followed by an immunotherapy which has no curative effect when administered alone. These results demonstrate the role of CD4(+)CD25(+) regulatory T cells in tumor-induced immune tolerance and the interest of regulatory T cell depletion to sensitize established tumors to immunotherapy.

Animals↗
PubMed2004

Intravascular malignant lymphomatosis diagnosed on a muscular biopsy: a case report.

Intravascular malignant lymphomatosis (IML) is characterized by proliferation of malignant lymphoid B cells within the lumens of small vessels. Common symptoms include general weakness and central neurological and cutaneous signs. Only histopathological analysis can confirm the diagnosis. We report on a 69-year-old man hospitalized for general weakness, inflammatory syndrome, and hemophagocytic syndrome (HS). Our observation shows that histopathological signs may be observed on a muscular biopsy without clinical or biological signs of muscular involvement.

Journal Article↗
PubMed2003

Freshly isolated bone marrow cells induce death of various carcinoma cell lines.

In some carcinomas such as digestive tract carcinomas, bone marrow infiltration by tumor cells is a frequent event but usually remains a micrometastatic disease and rarely induces overt bone lesions. The mechanisms responsible for the control of these metastases in the bone marrow remain poorly known. We show that freshly isolated bone marrow cells from human, murine and rat origin rapidly kill a wide range of syngeneic or xenogeneic carcinoma cell lines in culture. Further analysis of this cytotoxic process in the rat indicated that neither resident bone marrow macrophages nor NK cells were responsible for this cytotoxic effect that was restricted to a subpopulation of bone marrow cells expressing CD90 (Thy-1), a marker of hemopoietic precursors. The tumoricidal activity of these cells did not require long-term culture nor addition of exogenous cytokines or growth factors. A subset of CD90+ cells that rapidly differentiates into CD163(ED2)-expressing macrophages was observed to be responsible for tumor cell killing. These macrophages induced a non-apoptotic death of tumor cells, a process that required both a direct interaction with the tumor cell and nitric oxide (NO) production through the activation of inducible nitric oxide-synthase (iNOS). This ability of pluripotent hemopoietic stem cells to rapidly differentiate into macrophages capable of killing invasive tumor cells may account for the limited expansion of micrometastases of some carcinomas in the bone marrow.

Animals↗
PubMed2003

A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines.

Fusion of tumor cells with antigen-presenting cells (APCs) has been proposed for the preparation of cancer vaccines. However, generation of these hybrids, using physical or chemical methods such as electrofusion or polyethylene glycol (PEG), has been difficult to standardize. Characterization of cell fusion has also been problematic because of difficulties in differentiating fusion from cell aggregation, leakage of cellular dyes and dendritic-cell (DC) phagocytosis of tumor material. In this report, we describe a new method to generate hybrid cell vaccines, based on gene transfer of a viral fusogenic membrane glycoprotein (FMG) into tumor cells, and incorporate a genetic method by which true hybrid formation can be unambiguously detected. We describe a new class of tumor cell-DC hybrid that can be rapidly isolated after cell fusion. These hybrids are highly potent in in vitro antigen presentation assays, target lymph nodes in vivo and are powerful immunogens against established metastatic disease.

Animals↗
PubMed2003

Intradermal injection, as opposed to subcutaneous injection, enhances immunogenicity and suppresses tumorigenicity of tumor cells.

Tumor cell immunogenicity depends heavily upon the microenvironment in which the cells grow. We have compared the tumorigenicity and immunogenicity of the same tumor cells when injected either into the dermis, a tissue containing numerous dendritic cells (DCs), or s.c., at a site which contains only few DCs. After s.c. injection, progressive tumors were constantly obtained, whereas most intradermal injections did not give rise to tumor and immunized animals against additional challenge. We present evidence that the high density of DCs at dermal sites facilitates the capture of tumor antigens and that local inflammation induces maturation of the DCs and their migration into draining lymph nodes.

Adenocarcinoma↗
PubMed2003

[Acute-phase reaction].

The systemic changes induced by inflammation have been referred as the acute-phase response. The changes in the concentrations of acute-phase proteins are due largely to changes in their production by hepatocytes induced by pro-inflammatory cytokines. Because of its specificity, sensibility and short half-life, C-reactive protein is the most useful indicator among all the acute-phase proteins. The clinical strategy to deal with an acute-phase response is to search the aetiology: infections, neoplasms, auto-immune and allergic diseases. The treatment of an acute-phase response is the treatment of its aetiology.

Acute-Phase Proteins↗
PubMed2002

An atypical caspase-independent death pathway for an immunogenic cancer cell line.

REGb cell line, a highly immunogenic tumor cell variant isolated from a rat colon cancer, yields regressive tumors when injected into syngeneic hosts. We previously demonstrated that REGb tumor immunogenicity was related to the capacity of releasing dead cells in vivo. Also, in vitro, REGb cell monolayers release dead cells, especially when cultured in serum-free medium. In the current study, we show that the release of dead cells results from an atypical death process associating features of necrosis and apoptosis. In spite of features considered as hallmarks of caspase-dependent apoptosis, including chromatin fragmentation and DNA oligonucleosomal cleavage, caspases are not activated and caspase inhibitors are ineffective to prevent REGb cell death. In contrast with a number of other types of cell death, the spontaneous death of REGb cells in culture depends on de novo protein synthesis as this death is blocked by low doses of the mRNA translation inhibitor cycloheximide. This unusual mode of cell death that associates necrotic and apoptotic features could provide optimal conditions for triggering a specific immune response.

Amino Acid Chloromethyl Ketones↗