Tumor immunology meets oncology (TIMO) XVI, July 07-09 2022 in Halle/Saale, Germany.

During the TIMO meeting 2022, national and international scientists as well as clinicians gave novel insights as well as perspectives into basic and translational tumor immunology.

Tumor immunology meets oncology (TIMO) XVII, April 20-22 2023 in Halle/Saale, Germany.

During the TIMO meeting 2023, national and international scientists as well as clinicians gave novel insights as well as perspectives into basic and translational tumor immunology. https://dgfi.org/arbeitskreise/ak-tumorimmunologie/meeting/.

"Tumor immunology meets oncology (TIMO) XV", April 25th-27th 2019, Halle/Saale, Germany.

Novel insights into basic and translational tumor immunology including immunotherapies were presented by national and international scientists and clinicians at the TIMO XV meeting in Halle.

Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy.

Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.

Conventional CARs versus modular CARs.

The clinical application of immune effector cells genetically modified to express chimeric antigen receptors (CARs) has shown impressive results including complete remissions of certain malignant hematological diseases. However, their application can also cause severe side effects such as cytokine release syndrome (CRS) or tumor lysis syndrome (TLS). One limitation of currently applied CAR T cells is their lack of regulation. Especially, an emergency shutdown of CAR T cells in case of life-threatening side effects is missing. Moreover, targeting of tumor-associated antigens (TAAs) that are not only expressed on tumor cells but also on vital tissues requires the possibility of a switch allowing to repeatedly turn the activity of CAR T cells on and off. Here we summarize the development of a modular CAR variant termed universal CAR (UniCAR) system that promises to overcome these limitations of conventional CARs.

Natural killer cells control metastasis via structural editing of primary tumors in mice.

Natural killer (NK) cells are innate immune lymphocytes which express an array of activating and inhibitory receptors. These receptors bind a large spectrum of ligands, which are expressed on stressed, malignantly transformed or virally infected cells, as well as on bacterial, fungal, and parasitic pathogens. The decision on whether or not to kill the target is based on the integration of activating and inhibitory signals sent downstream from NK cell receptors. One of the most prominent NK cell activating receptor families is the family of natural cytotoxicity receptors (NCRs) which includes NKp30, NKp44, and NKp46. NKp46 is the only NCR to have a fully functional mouse orthologue denoted Ncr1. Despite a large body of evidence highlighting its importance in the clearance of both solid and liquid tumors, the membrane-bound tumor ligand for NKp46 and its mouse orthologue Ncr1 is still unknown. Here we review the discovery of a novel role for NKp46/Ncr1, not only in tumor clearance but also in prevention of metastasis by structural editing of primary tumors.

The role of immune infiltrates as prognostic biomarkers in patients with breast cancer.

The presence of immune infiltrates in the tumor microenvironment has been documented in many types of cancer. Moreover, the preexistent or endogenous immunity which consists of interactions between intratumoral lymphocytes and tumor cells is mostly relevant for the successful application of various anticancer therapies, including standard chemotherapy, immune checkpoint inhibition-based immunotherapy and targeted therapies. The immunoscore defines densities of intratumoral immune infiltrates which determine poor or favorable prognosis depending on their quantity and quality in the tumor compartments. Results from large clinical studies have demonstrated an association between high densities of cytotoxic and memory TILs in the tumor compartments with improved prognosis. Importantly, we have demonstrated that differential combined densities of immune infiltrates jointly analyzed in the tumor center (TC) and the invasive margin (IM) have a significant prognostic value in breast cancer patients with poor clinicopathological parameters.

Unlocking the therapeutic potential of primary tumor-draining lymph nodes.

Lymph nodes draining the primary tumor are essential for the initiation of an effective anti-tumor T-cell immune response. However, cancer-derived immune suppressive factors render the tumor-draining lymph nodes (TDLN) immune compromised, enabling tumors to invade and metastasize. Unraveling the different mechanisms underlying this immune escape will inform therapeutic intervention strategies to halt tumor spread in early clinical stages. Here, we review our findings from translational studies in melanoma, breast, and cervical cancer and discuss clinical opportunities for local immune modulation of TDLN in each of these indications.

Results of surgical treatment for juvenile myasthenia gravis. / Resultados del tratamiento quirúrgico en la miastenia gravis juvenil.

INTRODUCTION: Radical or extended thymectomy is an effective treatment for myasthenia gravis in the adult population. There are few reports to demonstrate the effectiveness of this treatment in patients with juvenile myasthenia gravis. OBJECTIVE: The main objective of this study was to show that extended transsternal thymectomy is a valid option for treating this disease in paediatric patients. RESULTS: Twenty-three patients with juvenile myasthenia gravis underwent this surgical treatment in the period between April 2003 and April 2014; mean age was 12.13 years and the sample was predominantly female. The main indication for surgery, in 22 patients, was the generalised form of the disease (Osserman stage II) together with no response to 6 months of medical treatment. The histological diagnosis was thymic hyperplasia in 22 patients and thymoma in one patient. There were no deaths and no major complications in the postoperative period. After a mean follow-up period of 58.87 months, 22 patients are taking no medication or need less medication to manage myasthenic symptoms. CONCLUSIONS: Extended (radical) transsternal thymectomy is a safe and effective surgical treatment for juvenile myasthenia gravis.

First-principles study of electronic structures and stability of body-centered cubic Ti-Mo alloys by special quasirandom structures.

The electronic structures and structural properties of body-centered cubic Ti-Mo alloys were studied by first-principles calculations. The special quasirandom structures (SQS) model was adopted to emulate the solid solution state of the alloys. The valence band electronic structures of Ti-Mo and Ti-Mo-Fe alloys were measured by hard x-ray photoelectron spectroscopy. The structural parameters and valence band photoelectron spectra were calculated using first-principles calculations. The results obtained with the SQS models showed better agreement with the experimental results than those obtained using the conventional ordered structure models. This indicates that the SQS model is effective for predicting the various properties of solid solution alloys by means of first-principles calculations.

Effect of luting system with acidic primers on the durability of bonds with Ti-15Mo-5Zr-3Al titanium alloy and its component metals.

This study evaluated the effect of luting system with acidic primers on the durability of bonds with Ti-15Mo-5Zr-3Al titanium alloy (Ti-15Mo-5Zr-3Al) and its component metals. Adherend metals were Ti-15Mo-5Zr-3Al, Ti, Mo, Zr, and Al. Four primers were evaluated as adhesion promoters: Alloy Primer (ALP), Estenia Opaque Primer (EOP), M. L. Primer (MLP), and Super Bond liquid (SBL). An acrylic resin was used as the luting material. Pre- and post-thermocycling shear bond strength was determined to evaluate the bonding durability, and the results were compared using non-parametric statistical analyses (n=11/group). The post-thermocycling bond strength in MPa (median) associated with ALP, EOP, MLP, and SBL were 18.8, 19.8, 4.1, and 0.8, respectively, for Ti-15Mo-5Zr-3Al. The results showed that two primers containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP) were effective for the durability of bonding of Ti-15Mo-5Zr-3Al to the resin. MDP enhanced the bonding durability of the resin bonded to either Ti, Zr, or Al.

Effect of Fluoride Content of Mouthwashes on the Metallic Ion Release in Different Orthodontics Archwires.

Metal ion release studies were carried out on three of the most commonly used orthodontic wires in the clinic: austenitic stainless steel, Ti-Mo, and superelastic NiTi, using three mouthwashes with different fluoride concentrations: 130, 200, and 380 ppm. Immersions were carried out in these mouthwashes at 37 °C for 1, 4, 7, and 14 days, and the ions released were determined by inductively coupled plasma-mass spectrometry (ICP-MS). All wires were observed by scanning electron microscopy (SEM). The results showed a moderate ion release in the stainless steel wires, with nickel and chromium values of 500 and 1000 ppb in the worst conditions for the wires: concentrations of 380 ppm fluoride and 14 days of immersion. However, in the Ti-Mo and NiTi alloys, an abrupt change in release was observed when the samples were immersed in 380 ppm fluoride concentrations. Titanium releases in Ti-Mo wires reached 200,000 ppb, creating numerous pits on the surface. Under the same conditions, the release of Ni and Ti ions from the superelastic wires also exceeded 220,000 ppb and 180,000 ppb, respectively. This release of ions causes variations in the chemical composition of the wires, causing the appearance of martensite plates in the austenitic matrix after 4 days of immersion. This fact causes it to lose its superelastic properties at a temperature of 37 °C. In the case of immersion in 380 ppm mouthwashes for more than 7 days, rich-nickel precipitates can be seen. These embrittle the wire and lose all tooth-correcting properties. It should be noted that the release of Ni ions can cause hypersensitivity in patients, particularly women. The results indicate that the use of mouthwashes with a high content of fluoride should not be recommended with orthodontic archwires.

Effect of Si Content on the Thermal Expansion of Ti15Mo(0-2 Si) Biomaterial Alloys during Different Heating Rates.

Thermal expansion measurements were used to characterize phase transformations in metastable ß-Ti alloys (Ti15MoxSi) without and with various Si additions (where x = 0, 0.5, 1.0, 1.5, and 2 in wt.%) during linear heating at two heating rates of 5 and 10 °C/min up to 850 °C. For this study, five alloys were developed and examined in terms of their presence phases, microstructures, and starting and final transformation temperatures. According to the results, all of the as-cast samples primarily include an equiaxed ß-Ti phase. The influence of phase transformation on the material dimensions was discussed and compared with the variations in Si contents. The transformation was investigated using a dilatometric technique for the developed alloys during continuous heating and cooling. The dilatometric curve of heating revealed two distinct reflection points as the heating temperature increased. The starting transformation temperature (Ts) to obtain the ω-phase was reported at 359 °C without Si addition; whereas the final transformation temperature (Tf) of the dissolution of α-phase was obtained at 572 °C at a heating rate of 10 °C/min. At 2 wt.% Si, the first derivative curves reported Ts and Tf transforming temperatures of 314-565 °C (at a 5 °C/min heating rate) and 270-540 °C (at a 10 °C/min heating rate), respectively. The Ts and Tf transforming temperatures were significantly decreased with Si additions, which decreased the ß-transus temperature. Moreover, the thermal expansion coefficient curves of the investigated alloys without and with 2 wt.% Si were studied. The transformation heating curves have an S-shaped pattern, according to the results.

[Myasthenia gravis. Update on diagnosis and therapy]. / Miastenia gravis. Actualización diagnóstica y terapéutica.

Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and is clinically characterized by the presence of fatigueable muscle weakness. In the etiopathogenesis plays a central role the thymus and the most frequently detected pathogenic autoantibodies are targeted to the acetylcholine receptor. The increase in the knowledge of the immunological components of the neuromuscular junction in the last two decades has been fundamental to identify new pathogenic antibodies, reduce the percentage of patients with seronegative myasthenia, and propose a classification of patients into subgroups with clinical-therapeutic interest. In addition, in recent years, new drugs have been developed for the treatment of patients with myasthenia gravis that are refractory to conventional immunosuppressive treatment.

Imaging palpable tumors in pediatrics: Part 2.

Palpable tumors in children are a common reason for consulting a radiologist. The origin of these lesions varies widely, and although they are common, classic radiology books do not cover some of them. This series of two articles aims to review the clinical and radiological characteristics of a selection of palpable tumors in children that radiologists need to be familiar with.

[Intrathyroidal thymus can cause confusion in the diagnosis of a thyroid mass. A case report]. / Timo intratiroideo: una causa de confusión en el diagnóstico de masas tiroideas infantiles. Reporte de caso.

Intrathyroidal thymus tissue (ITTT) is a rare, benign condition; its diagnosis can prove challenging due to unfamiliarity with this entity. However, it has ultrasonographical and cytological characteristics which can suggest its presence and thus should be considered in the differential diagnosis of thyroid nodules. Presently, immunohistochemistry can be used with fine needle aspiration (FNA) cytology, thus decreasing the need for unnecessary surgery. We discuss the usefulness of immunohistochemistry in thyroid cytology, with reference to a case of a 10-year-old patient, who underwent partial thyroidectomy for a suspicious thyroid nodule which was eventually diagnosed as ITTT by the histopathology of the surgical specimen.

Echographic findings in ectopic intrathyroidal thymic tissue in children. A systematic review.

Intrathyroidal ectopic thymic tissue (IETT) is an indulgent, unusual entity and is part of the differential diagnosis of thyroid nodules in the pediatric population. Because of the low prevalence of IETT, the diagnosis may be difficult. Awareness of this diagnosis is definitive to avoid surgical interventions. The aim of this study was to review the literature on the echographic characteristics of IETT. We conducted a search of Ovid, PubMed and the virtual health library. A total of 619 patients with a mean age of 6.2 years old were included. IETT was located in the lower portion of both of the thyroidal lobes in 556 children, the echographic shape was reported for 173 patients, with the fusiform shape as the most representative, the appearance of the IETTs was reported for 121 patients, the most common was the hypoechogenic pattern with multiple internal echogenic foci. The average lesion diameter was 5.53 mm, and Doppler findings reported a hipovascular pattern in 56% of the lesions. In conclusion, IETT is an infrequent entity; nonetheless, it must be considered in the differential diagnosis of neck nodules in children and should be study and follow with echography to avoid unnecessary surgery.

Evidence for spinodal decomposition in Ti-15Mo quenched alloy using transmission electron microscopy.

Electron diffraction effect associated with nano-scale periodic modulations observed in a quenched Ti-15 wt%Mo alloy within ω phase forming regime has been investigated in this study by analyzing selected area diffraction patterns and high-resolution phase contrast images. Crystallographic direction of the side bands in electron diffraction associated with the periodic modulation of wavelength 1.3 nm is established as [001]ß which is an elastically soft direction for the body-centered cubic lattice. Characteristics of the side bands in the diffraction patterns, such as the correlation of spacing of satellite spots with real-space modulation wavelength and the constancy in the direction of satellites and modulations are interpreted as the proof of phase separation by spinodal decomposition. The striations associated with spinodal decomposition form only in Mo-enriched regions of dimensions ˜ 20 nm distributed throughout the ß matrix. Accordingly, in this study, two varieties of compositional modulations that appear in the matrix are experimentally illustrated: (1) Mo-depleted and Mo-enriched domains of 10-20 nm size, and (2) The anisotropic compositional modulation by spinodal decomposition in [001]ß direction with a modulation wavelength of 1.3 nm occurring in Mo-enriched pockets. It is confirmed that the structural modulations and ω phase formation occurs only in the regions without striations (Mo-lean regions). By analyzing the diffraction spots, it is also shown that the ω phase does not undergo any phase separation by spinodal decomposition.