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Cécile Badoual

Publications and source records attributed to Cécile Badoual.

13 recordsLinked to original sources

The immune paradox of sarcoidosis and regulatory T cells.

Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25(bright)FoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-alpha production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.

Adult↗

Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers.

PURPOSE: CD4(+) T cells play a central role in initiating and maintaining anticancer immune responses. However, regulatory CD4(+)CD25(+) T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells. In view of these heterogeneous CD4(+) T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4(+) T-cell populations in head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study. Double or triple immunofluorescence staining was done to assess and quantify the activated CD4(+)CD69(+) T cells, regulatory CD4(+)Foxp3(+) T cells, and mixed CD4(+)CD25(+) T cells comprising both activated and regulatory T cells. RESULTS: On univariate analysis, high levels of tumor-infiltrating CD4(+)CD69(+) T cells were correlated with both better locoregional control (P = 0.01) and longer survival (P = 0.01). Infiltration by regulatory Foxp3(+)CD4(+) T cells was positively associated with a better locoregional control of the tumor. Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage (P = 0.02) and CD4(+)Foxp3(+) T-cell infiltration of the tumor (P = 0.02). In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage (P = 0.036) and CD4(+)CD69(+) T-cell infiltration (P = 0.017). CONCLUSION: This study shows that tumor-infiltrating activated CD4(+)CD69(+) T cells are associated with a good prognosis in head and neck squamous cell carcinoma. In addition, regulatory Foxp3(+)CD4(+) T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression.

Antigens, CD↗

Global natural regulatory T cell depletion in active systemic lupus erythematosus.

The immune defect that could account for the multisystemic involvement that characterizes systemic lupus erythematosus (SLE) remains unknown. We hypothesized that iterative disease flares correspond to a recurrent defect in the peripheral immune suppression exerted by naturally occurring T regulatory cells (Tregs). Surprisingly, Tregs isolated from lupus patients show the same phenotypic and functional characteristics as corresponding cells found in healthy controls. A decrease in the proportion of circulating Tregs among other CD4+ T cells is nevertheless evidenced in active patients when this group is compared with healthy controls (0.57 +/- 0.24%, n = 45 vs 1.29 +/- 0.38%, n = 82, p < 0.0001) or with inactive patients (1.22 +/- 0.67%, n = 62, p < 0.0001). In contrast, the proportion of Tregs in other systemic autoimmune diseases such as primary Sjögren syndrome and inflammatory myopathy does not significantly differ from controls' values (1.15 +/- 0.46%, n = 21, p = 0.09 and 1.16 +/- 0.44%, n = 16, p = 0.43, respectively). Lupus Tregs do not accumulate in either the lymph nodes or the diseased kidneys and are not killed by a circulating soluble factor, but demonstrate in vitro a heightened sensitivity to Fas-induced apoptosis. Finally, we show that the extent of Treg depletion correlates with the clinical severity of the flare. SLE flares are therefore associated with a global Treg depletion and not with a phenomenon of tissue redistribution. In summary, we suggest that the physiopathology of SLE could be tied to a defect in the homeostatic control of the Treg subpopulation.

Adolescent↗

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is usually associated with a chronic inflammatory disease from which lymphoid tissue of MALT type arises as a prerequisite for lymphoma proliferation. No well-characterized chronic inflammatory process has been identified in the larynx. METHODS: We report a case of primary MALT lymphoma of the larynx associated with extraesophageal reflux, chronic laryngitis, and gastric Helicobacter pylori infection, raising the issue of its physiopathology and treatment. RESULTS: Treatment of this MALT lymphoma of the larynx consisted of complete surgical excision associated with omeprazole, amoxicillin, and clarithromycin. No evidence of disease was observed after 24 months of follow-up. CONCLUSIONS: We may assume that chronic laryngitis could be a precursor to MALT lymphoma. This case is the first one to our knowledge of a primary MALT lymphoma of the larynx treated with conservative management combining surgical excision, reflux therapy, and eradication of gastric H. pylori infection.

Humans↗

[Phenotypic and functional analysis of T lymphocytes in cancer patients].

In preclinical tumor model and in human cancer, tumor antigen specific T lymphocytes play a key role in the control of tumor development. Nevertheless in numerous cases, the infiltrating tumor T cells do not seem to influence the clinical progression of the tumor. A better phenotypic and functional characterization of T cells in close contact with tumor associated with a comprehensive analysis of tumor evasion mechanism to the host response should lead to an optimization of cancer immunotherapy protocols.

Antigens, CD↗

[Mycoses of the head and neck].

In recent years, mycoses have emerged as important infections in clinical practice. This phenomenon is explained by the ever growing number of immunocompromised patients and the increasing number of people travelling in areas where fungal diseases are endemic. Head and neck infections are common in disseminated mycoses and may simulate carcinoma or cause upper airway obstruction. The most frequent causative yeasts or yeast-like organisms include Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum var capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Coccidioides immitis. Other causative fungal pathogens include Aspergillus fumigatus and less frequently, Rhizopus oryzae and Rhinosporidium seeberi. Since in most cases their pathophysiology is similar, those microorganisms share a common clinical pathological presentation. Symptoms such as dysphonia or dysphagia associated with hyperplastic and ulcerative lesions on endoscopic examination should prompt biopsies. A purulent or granulomatous inflammatory tissue reaction with pseudoepitheliomatous hyperplasia warrants caution since it may lead to a mistaken diagnosis of carcinoma. The pathologist must look carefully for microorganisms with Grocott and PAS stains. The causative agent can be identified if the pathologist is aware of the risk. Positive culture is needed to institute adequate treatment.

Aspergillosis↗

Metastatic thoracic lymph node carcinoma with unknown primary site.

BACKGROUND: Metastatic cancer in thoracic lymph nodes without a primary site is rare. The purpose of this study is to draw attention to this probably underestimated entity, to speculate on its possible origins, and to suggest guidelines for its treatment. METHODS: Eight heavy smokers with no past medical history of cancer were diagnosed at operation to have malignant cells in intrathoracic lymph nodes (N1 or N2) with no primary site in the lung. All patients underwent an exploratory thoracotomy with a presumed diagnosis of lung cancer except one who presented with a middle lobe mucosa-associated lymphoid tissue lymphoma. We reviewed the type of surgical resection, histologic and immunohistochemical analysis of resected specimens, treatments, survival, and long-term results. RESULTS: Resections performed were pneumonectomy (n = 4), lobectomy (n = 3), and bilobectomy (n = 1). All patients underwent complete mediastinal lymph node dissection. Lung resection was performed for mucosa-associated lymphoid tissue lymphoma (n = 1) and for tumorlike lesions that appeared to be tuberculoma (n = 1) and intrapulmonary metastatic lymph nodes (n = 6). Malignant cells were located in intrapulmonary lymph nodes alone (n = 3) or also in mediastinal lymph nodes in three other cases. All these tumors were cytokeratin-positive, demonstrating their epithelial nature. Pulmonary origin was confirmed in two cases (thyroid transcription factor 1-positive and thyroglobulin-negative). No other origin could be demonstrated by immunochemistry. Three patients died within the first year. All other patients are still alive without recurrence (Kaplan-Meier 5-year survival rate, 62.5%). CONCLUSIONS: Frequency of metastatic cancer in thoracic lymph nodes without a primary site is probably underestimated because the cancer is routinely diagnosed by mediastinoscopy and considered as metastatic disease not amenable to operation. The origin of the disease, either pulmonary, endogenous, or from extrathoracic sites, is often difficult to assess. Nevertheless, our data confirm those of the literature and demonstrate that survival can be increased by operation. This implies diagnosis of the entity and consideration that thoracic lymph node involvement can apparently be isolated and therefore resectable.

Aged↗

Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal.

BACKGROUND: Despite an early-stage diagnosis, lung cancer presenting with visceral pleura invasion (VPI) or malignant pleural lavage cytology (PLC) has a poor prognosis. The purpose of this study was to correlate VPI to malignant PLC. METHODS: One hundred forty-three consecutive patients scheduled for surgical lung resection having undergone preresectional pleural lavage cytology were reviewed. There were 121 malignant and 22 nonmalignant lesions. All cases were studied by pathology, histology, previous transthoracic puncture, VPI, and presence of pleural lymphatic involvement. RESULTS: PLC was positive (n = 13) or suspected (n = 5) for malignant cells in, respectively, 10.7% and 4.1% of patients with lung cancer. There was no positive PLC in cases of nonmalignant disease. PLC was positive only in pT2 tumors and almost always when the tumor was exposed on the pleural surface, thus possibly exfoliating within the pleural space (12/17 patients, 70.6%; p < 0.01). Positive PLC was obtained whatever the histology but did not appear related to previous transthoracic puncture or involvement of pleural lymphatics by tumor cells. CONCLUSIONS: VPI and positive PLC are linked, and the appearance of tumor cells within the pleural cavity can be explained by tumor desquamation. The role that visceral pleura involvement and parietal pleura reabsorption play in lung cancer is of paramount importance and deserves further research. A better understanding of their relationship could have major implications in the therapeutic management of non-small cell lung cancer.

Adenocarcinoma↗

[Bladder amyloidosis. Report of two cases].

Bladder amyloidosis is a rare disease. The clinical features cannot be distinguished from those of urothelial tumours. The authors report two cases of type AL bladder amyloidosis associated with multiple myeloma and discuss the aetiology, histology and clinical course of this disease.

Aged↗

[Cytotoxic T lymphocytes: role in immunosurveillance and in immunotherapy].

Experiments in mice and recent human clinical studies have clearly shown the contribution of CD8+ T lymphocyte in the control of tumor development. CD8+ T lymphocytes are a constitutive component of the immune response during the development of cancer. In murine models, the efficiency of various cancer vaccines mainly depends on their ability to induce CD8+ T lymphocytes. Clinical responses in immunotherapy treated cancer patients have been associated with the presence of antitumor specific CD8+ T lymphocytes. In spontaneous regressive melanomas, intratumor antigen specific CD8+ cytotoxic T cells were expanded suggesting their involvement in the tumor shrinkage. Administration of antitumor specific cytotoxic T clones in mice resulted in antitumor responses which directly demonstrated the therapeutic efficiency of these cells. However, in most cases during cancer progression, the presence of antitumor CD8 T lymphocyte is not associated with clinical responses. Intrinsic functional abnormalities of these cells or a defect of CD8+ T cell migration to the tumor may in part explain their failure to inhibit tumor development. On the other hand, tumors also develop immune escape mechanisms (down modulation of tumor antigens, secretion of immunosuppressive factors, expression of anti-apoptotic molecules by the tumors, or pro-apoptotic factors inducing T cell death) to resist to the CD8+ T cell attack. To circumvent these tumor escape mechanisms, efficient cancer vaccines will have to recruit CD8+ T cells associated with other immune effectors.

Animals↗