Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study.

Background: This study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. Patients and Methods: Data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. Results: Sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. Conclusions: Combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.

Integration of Bridge Damage Detection Concepts and Components (3 volumes), TR-636, 2013

This work is divided into three volumes: Volume I: Strain-Based Damage Detection; Volume II: Acceleration-Based Damage Detection; Volume III: Wireless Bridge Monitoring Hardware. Volume I: In this work, a previously-developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The statistical damage-detection tool, control-chart-based damage-detection methodologies, were further investigated and advanced. For the validation of the damage-detection approaches, strain data were obtained from a sacrificial specimen attached to the previously-utilized US 30 Bridge over the South Skunk River (in Ames, Iowa), which had simulated damage,. To provide for an enhanced ability to detect changes in the behavior of the structural system, various control chart rules were evaluated. False indications and true indications were studied to compare the damage detection ability in regard to each methodology and each control chart rule. An autonomous software program called Bridge Engineering Center Assessment Software (BECAS) was developed to control all aspects of the damage detection processes. BECAS requires no user intervention after initial configuration and training. Volume II: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The objective of this part of the project was to validate/integrate a vibration-based damage-detection algorithm with the strain-based methodology formulated by the Iowa State University Bridge Engineering Center. This report volume (Volume II) presents the use of vibration-based damage-detection approaches as local methods to quantify damage at critical areas in structures. Acceleration data were collected and analyzed to evaluate the relationships between sensors and with changes in environmental conditions. A sacrificial specimen was investigated to verify the damage-detection capabilities and this volume presents a transmissibility concept and damage-detection algorithm that show potential to sense local changes in the dynamic stiffness between points across a joint of a real structure. The validation and integration of the vibration-based and strain-based damage-detection methodologies will add significant value to Iowa’s current and future bridge maintenance, planning, and management Volume III: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. This report volume (Volume III) summarizes the energy harvesting techniques and prototype development for a bridge monitoring system that uses wireless sensors. The wireless sensor nodes are used to collect strain measurements at critical locations on a bridge. The bridge monitoring hardware system consists of a base station and multiple self-powered wireless sensor nodes. The base station is responsible for the synchronization of data sampling on all nodes and data aggregation. Each wireless sensor node include a sensing element, a processing and wireless communication module, and an energy harvesting module. The hardware prototype for a wireless bridge monitoring system was developed and tested on the US 30 Bridge over the South Skunk River in Ames, Iowa. The functions and performance of the developed system, including strain data, energy harvesting capacity, and wireless transmission quality, were studied and are covered in this volume.

Coronary magnetic resonance angiography in adolescents and young adults with kawasaki disease.

BACKGROUND: In patients with Kawasaki disease, serial evaluation of the distribution and size of coronary artery aneurysms (CAA) is necessary for risk stratification and therapeutic management. Although transthoracic echocardiography is often sufficient for this purpose initially, visualization of the coronary arteries becomes progressively more difficult as children grow. We sought to prospectively compare coronary magnetic resonance angiography (MRA) and x-ray coronary angiography findings in patients with CAA caused by Kawasaki disease. METHODS AND RESULTS: Six subjects (age 10 to 25 years) with known CAA from Kawasaki disease underwent coronary MRA using a free-breathing T2-prepared 3D bright blood segmented k-space gradient echo sequence with navigator gating and tracking. All patients underwent x-ray coronary angiography within a median of 75 days (range, 1 to 359 days) of coronary MRA. There was complete agreement between MRA and x-ray angiography in the detection of CAA (n=11), coronary artery stenoses (n=2), and coronary occlusions (n=2). Excellent agreement was found between the 2 techniques for detection of CAA maximal diameter (mean difference=0.4 +/- 0.6 mm) and length (mean difference=1.4 +/- 1.6 mm). The 2 methods showed very similar results for proximal coronary artery diameter (mean difference=0.2 +/- 0.5 mm) and CAA distance from the ostia (mean difference=0.1 +/- 1.5 mm). CONCLUSION: Free-breathing 3D coronary MRA accurately defines CAA in patients with Kawasaki disease. This technique may provide a non-invasive alternative when transthoracic echocardiography image quality is insufficient, thereby reducing the need for serial x-ray coronary angiography in this patient group.

Afatinib versus placebo as adjuvant therapy after chemoradiation in a double-blind, phase III study (LUX-Head & Neck 2) in patients with primary unresected, clinically intermediate-to-high-risk head and neck cancer: study protocol for a randomized controlled trial.

BACKGROUND: Over 50% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced disease. Those at intermediate-to-high risk of recurrence after definitive therapy exhibit advanced disease based on tumour size or lymph node involvement, non-oropharynx primary sites, human papillomavirus (HPV)-negative oropharyngeal cancer, or HPV-positive oropharynx cancer with smoking history (>10-pack-years). Non-surgical approaches include concurrent chemoradiotherapy, induction chemotherapy followed by definitive radiotherapy or chemoradiotherapy, or radiotherapy alone. Following locoregional therapies (including surgical salvage of residual cervical nodes), no standard intervention exists. Overexpression of epidermal growth factor receptor (EGFR), an ErbB family member, is associated with poor prognosis in HNSCC. EGFR-targeted cetuximab is the only targeted therapy that impacts overall survival and is approved for HNSCC in the USA or Europe. However, resistance often occurs, and new approaches, such as targeting multiple ErbB family members, may be required. Afatinib, an irreversible ErbB family blocker, demonstrated antiproliferative activity in preclinical models and comparable clinical efficacy with cetuximab in a randomized phase II trial in recurrent or metastatic HNSCC. LUX-Head & Neck 2, a phase III study, will assess adjuvant afatinib versus placebo following chemoradiotherapy in primary unresected locoregionally advanced intermediate-to-high-risk HNSCC. METHODS/DESIGN: Patients with primary unresected locoregionally advanced HNSCC, in good clinical condition with unfavourable risk of recurrence, and no evidence of disease after chemoradiotherapy will be randomized 2:1 to oral once-daily afatinib (40 mg starting dose) or placebo. As HPV status will not be determined for eligibility, unfavourable risk is defined as non-oropharynx primary site or oropharynx cancer in patients with a smoking history (>10 pack-years). Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. The primary endpoint measure is duration of disease-free survival; secondary endpoint measures are disease-free survival rate at 2 years, overall survival, health-related quality of life and safety. DISCUSSION: Given the unmet need in the adjuvant treatment of intermediate-to-high-risk HNSCC patients, it is expected that LUX-Head & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve disease-free survival, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345669.

A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors.

PURPOSE: Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available. EXPERIMENTAL DESIGN: On the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell-derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non-small cell lung carcinoma (NSCLC); 513 colorectal; and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin-embedded tissue of 330 breast cancer patients. The cell types were identified with immunohistochemical costaining and confocal fluorescence microscopy. RESULTS: We identified immunoglobulin κ C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n = 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n = 845; P < 0.001). In addition, IGKC gene expression was prognostic in NSCLC and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin-embedded tissues of 330 breast cancer patients. Tumor-infiltrating plasma cells were identified as the source of IGKC expression. CONCLUSION: Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

In vivo effects of a recombinant vaccinia virus expressing a mouse mammary tumor virus superantigen.

Early after infection, the mouse mammary tumor virus (MMTV) expresses a superantigen (SAg) at the surface of B lymphocytes. Interaction with the T-cell receptor Vbeta domain induces a polyclonal proliferative response of the SAg-reactive T cells. Stimulated T cells become anergic and are deleted from the T-cell repertoire. We have used a recombinant vaccinia virus encoding the MMTV(GR) SAg to dissect the effects of the retroviral SAg during an unrelated viral infection. Subcutaneous infection with this recombinant vaccinia virus induces a very rapid increase of Vbeta14 T cells in the draining lymph node. This stimulation does not require a large Plumber of infectious particles and is not strictly dependent on the expression of the major histocompatibility complex class II I-E molecule, as it is required after MMTV(GR) infection. In contrast to MMTV infection during which B cells are infected, we do not observe any clonal deletion of the reactive T cells following the initial stimulation phase. Our data show that contrary to the case with MMTV, macrophages but not B cells are the targets of infection by vaccinia virus in the lymph node, indicating the ability of these cells to present a retroviral SAg. The altered SAg expression in a different target cell observed during recombinant vaccinia virus infection therefore results in significant changes in the SAg response.

In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.

In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vbeta4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vbeta4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vbeta4 Valpha8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vbeta4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vbeta4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vbeta4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.

Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans.

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node-like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin(+) T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell-rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter-CXCL13-transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell-rich zone.

Elicitation of specific cytotoxic T cells by immunization with malaria soluble synthetic polypeptides.

We have studied the immunogenicity of Plasmodium falciparum circumsporozoite (CS) protein-derived synthetic polypeptides in mice. These synthetic peptides correspond to the N- and the C-terminal domains 22-125 and 289-390, respectively of the P. falciparum 7G8 isolate CS protein expressed on the sporozoite surface. They comprise what is believed to be the mature protein, except for the central repetitive B cell domain. BALB/c (H-2d) mice were immunized s.c. with 50 micrograms soluble CS polypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resultant CTLs obtained by in vitro restimulation of primed lymph node (LN) cells recognized H-2Kd target cells in the presence of short synthetic peptides defined in the present study. These epitopes are contained within the N- and C-terminal regions of the CS protein, and correspond to sequences 39-47 and 333-342. In addition, these CTLs can specifically lyse H-2d target cells transfected with the CS gene. These results suggest that, by immunization of mice with large soluble CS synthetic polypeptides in IFA, it is possible to obtain MHC class I-restricted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vaccines.

Differential expression of NLRP3 among hematopoietic cells.

Although the importance of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in health and disease is well appreciated, a precise characterization of NLRP3 expression is yet undetermined. To this purpose, we generated a knock-in mouse in which the Nlrp3 coding sequence was substituted for the GFP (enhanced GFP [egfp]) gene. In this way, the expression of eGFP is driven by the endogenous regulatory elements of the Nlrp3 gene. In this study, we show that eGFP expression indeed mirrors that of NLRP3. Interestingly, splenic neutrophils, macrophages, and, in particular, monocytes and conventional dendritic cells showed robust eGFP fluorescence, whereas lymphoid subsets, eosinophils, and plasmacytoid dendritic cells showed negligible eGFP levels. NLRP3 expression was highly inducible in macrophages, both by MyD88- and Trif-dependent pathways. In vivo, when mice were challenged with diverse inflammatory stimuli, differences in both the number of eGFP-expressing cells and fluorescence intensity were observed in the draining lymph node. Thus, NLRP3 levels at the site of adaptive response initiation are controlled by recruitment of NLRP3-expressing cells and by NLRP3 induction.

Effect of soil interacting herbicides on soybean nodulation in Balcarce, Argentina

Two trials were performed in Balcarce, Argentina (37° 45' LS; 58° 18' LW) during 1993-94, to assess the effect of eight herbicides applied individually or in tank mixtures, on nodule number, nodule dry weight, seed yield and N percent in seed in soybean Asgrow 3205, inoculated with Bradyrhizobium japonicum CB 1809. Individual herbicides and doses in kg ha-1 of a.i. were metribuzin (0.48), acetochlor (0.90), metolachlor (1), flumioxazin (0.075), trifluralin (0.96), imazaquin (0.20), imazethapyr (0.10) and chlorimuron ethyl (0.0125). The mixtures were metribuzin+acetochlor (0.48+0.9), flumioxazin+acetochlor (0.075+0.9), imazaquin+acetochlor (0.2+0.9), metribuzin+metolachlor (0.48+1.92), and flumioxazin+ metolachlor (0.075+1.92). A control treatment without herbicides was included. Both trials were laid out as randomized complete blocks with four replicates, on a loam illitic thermic petrocalcic Paleudoll, 5.7% organic matter (OM), 25% clay, 30.4 cmol kg-1 CEC. Nodules were sampled at V2 (second node), V6 (sixth node) and R5 (beginning seed) growth stages. Herbicides did not significantly affect the beginning of nodulation or nodule number and mass at R5, not either grain yield or N accumulation. This indicates lack of interference between soil interacting herbicides and N fixation in the high organic matter, loam soils of SE Buenos Aires province, even though a tendency in less number and dry weight of nodules was evident at the two latter growth stages.

The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO - Young Members Working Group (AIRO Giovani).

Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO - Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.

Management of adenoid cystic carcinoma of the breast: a Rare Cancer Network study.

BACKGROUND: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC.¦METHODS: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy).¦RESULTS: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT.¦CONCLUSION: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

Lymphoid stroma in health and disease

Summary Secondary lymphoid organs (SLOB), such as lymph nodes and spleen, are the sites where primary immune responses are initiated. T lymphocytes patrol through the blood and SLOs on the search for pathogens which are presented to them as antigens by dendritic cells. Stromal cells in the Tzone - so called T zone fibroblastic reticular cells (TRCs) -are critical in organizing the migration of T cells and dendritic cells by producing the chemoattractants CCL19 and CCL21 and by forming a network which T cells use as a guidance system. They also form a system of small channels or conduits that allow rapid transport of small antigen molecules or cytokines from the subcapsular sinus to high endothelial venules. The phenotype and function of TRCs have otherwise remained largely unknown. We found a critical role for lymph node access in CD4+ and CD8+ T cell homeostasis and identified TRCs within these organs as the major source of interleukin-7 (IL-7). IL-7 is an essential survival factor for naïve T lymphocytes of which the cellular source in the periphery had been poorly defined. In vitro, TRC were able to prevent the death of naïve T but not of B lymphocytes by secreting IL-7 and the CCR7 ligand CCL 19. Using gene-targeted mice, we show anon-redundant function of CCL19 in T cell homeostasis. The data suggest that TRCs regulate T cell numbers by providing a limited reservoir of survival factors for which T cells have to compete. They help to maintain a diverse T cell repertoire granting full immunocompetence. To determine whether TRCs also play a role in pathology, we characterized so-called tertiary lymphoid organs (TLOs) that often develop at sites of chronic inflammation. We show that TLOs resemble lymph nodes or Peyer's patches not only with regard to lymphoid cells. TLOs formed extensive TRC networks and a functional conduit system in all three marine inflammation models tested. In one model we dissected the cells and signals leading to the formation of these structures. We showed that they critically depend on the presence of lymphotoxin and lymphoid tissue inducer cells. TRCs in TLOs also produce CCL19, GCL21 and possibly IL-7 which are all involved in the development of TLOs. Stromal cells therefore play a central role in the onset and perpetuation of chronic inflammatory diseases and could be an interesting target for therapy. Résumé Le système immunitaire est la défense de notre corps contre toutes sortes d'infections et de tumeurs. II est constitué de différentes populations de lymphocytes qui patrouillent constamment le corps à la recherche de pathogène. Parmi eux, les lymphocytes T et B passent régulièrement dans les organes lymphoïdes secondaires (SLO) qui sont les sites d'initiation de la réponse immunitaire. Les lymphocytes T sont recrutés du sang aux SLO où ils cherchent leur antigène respectif présenté par des cellules dendritiques. Des cellules stromales dans la zone T -nommées fibroblastic reticular cells' (TRC) -sécrètent des chimiokines CCL19 et CCL21 et ainsi facilitent les rencontres entre lymphocytes T et cellules dendritiques. De plus, elles forment un réseau que les lymphocytes T utilisent comme système de guidage. Ce réseau forme des petits canaux (ou conduits) qui permettent le transport rapide, d'antigène soluble ou de cytokines, de la lymphe aux veinules à endothelium épais (HEV). Le phénotype ainsi que les autres fonctions des TRCs demeurent encore à ce jour inconnus. Nous avons trouvé que l'accès des lymphocytes T CD4+ et CD8+ aux ganglions joue un rôle central pour l'homéostasie. Interleukin-7 (IL-7) est un facteur de survie essentiel pour les lymphocytes T naïfs dont la source cellulaire dans la périphérie était mal définie. Nous avons identifié les TRCs dans les ganglions comme source principale d'interleukin-7 (IL-7). In vitro, les TRCs étaient capable de prévenir la mort des lymphocytes T mais pas celle de lymphocytes B grâce à la sécrétion d'IL-7 et de CCL19. En utilisant des souris déficientes du gène CCL19, nous avons observé que l'homéostasie des lymphocytes T dépend aussi de CCL19 in vivo. Les données suggèrent que les TRCs aident à maintenir un répertoire large et diversifié de cellules T et ainsi l'immunocompétence. Pour déterminer si les TRCs pourraient jouer un rote également dans la pathologie, nous avons caractérisé des organes lymphoïdes tertiaires (TLOs) souvent associés avec l'inflammation chronique. Les TLOs ressemblent à des ganglions ou des plaques de Peyer pas seulement en ce qui concerne la présence de lymphocytes. Nous avons constaté que les TLOs forment des réseaux de TRC et un système fonctionnel de conduits. La formation de ces structures est fortement diminuée dans l'absence du signal lymphotoxin ou des cellules connues comme ymphoid tissue-inducer tells: Les TRCs dans les TLOs produisent les chimiokines CCL19, CCL21 et possiblement aussi IL-7 qui sont impliquées dans le développement des TLOs. Les cellules stromales jouent donc un rôle central dans l'initation et la perpétuation des maladies inflamatoires chroniques et pourraient être une cible intéressante pour la thérapie.