Leveraging spatial omics for the development of precision sarcoma treatments.

Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery. Limited knowledge of the sarcoma tumor microenvironment (TME) and of well-defined target antigens in the different subtypes necessitates an alternative investigative approach to improve treatments. Recent advances in spatial omics technologies have enabled a more comprehensive study of the TME in multiple cancers. In this opinion article we discuss advances in our understanding of the TME of some cancers enabled by spatial omics technologies, and we explore how these technologies might advance the development of precision treatments for sarcoma, especially pediatric sarcoma.

Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis.

Objectives: Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples. Methods: In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias. Results: We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56dimCD16+CD57- NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells. Conclusion: We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.

Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA.

CD3-engaging bispecific antibodies (BsAbs) have emerged as powerful therapeutic approaches by their ability to redirect T cells to eliminate tumor cells in a major histocompatibility complex-independent manner. However, how we can potentiate the efficacy of BsAbs remains largely unknown. To address this question, we investigated immunological mechanisms of action of a BsAb cotargeting CD3 and B-cell maturation antigen (BCMA) in syngeneic preclinical myeloma models. Treatment with the CD3/BCMA BsAb stimulated multiple CD3-expressing T-cell subsets and natural killer (NK) cells in the myeloma bone marrow (BM), highlighting its broad immunostimulatory effect. Notably, the BsAb-mediated immunostimulatory and antitumor effects were abrogated in mice lacking invariant NKT (iNKT) cells. Mechanistically, activation of iNKT cells and interleukin-12 production from dendritic cells (DCs) were crucial upstream events for triggering effective antitumor immunity by the BsAb. Myeloma progression was associated with a reduced number of BM iNKT cells. Importantly, the therapeutic efficacy of a single dose of CD3/BCMA BsAb was remarkably augmented by restoring iNKT cell activity, using adoptive transfer of α-galactosylceramide-loaded DCs. Together, these results reveal iNKT cells as critical players in the antitumor activity of CD3 engaging BsAbs and have important translational implications.

Electromagnetic diagnostic system for the Keda Torus eXperiment.

A system for electromagnetic measurements was designed and installed on the Keda Torus eXperiment (KTX) reversed field pinch device last year. Although the unique double-C structure of the KTX, which allows the machine to be opened easily without disassembling the poloidal field windings, makes the convenient replacement and modification of the internal inductive coils possible, it can present difficulties in the design of flux coils and magnetic probes at the two vertical gaps. Moreover, the KTX has a composite shell consisting of a 6 mm stainless steel vacuum chamber and a 1.5 mm copper shell, which results in limited space for the installation of saddle sensors. Therefore, the double-C structure and composite shell should be considered, especially during the design and installation of the electromagnetic diagnostic system (EDS). The inner surface of the vacuum vessel includes two types of probes. One type is for the measurement of the global plasma parameters, and the other type is for studying the local behavior of the plasma and operating the new saddle coils. In addition, the probes on the outer surface of the composite shell are used for measurements of eddy currents. Finally, saddle sensors for radial field measurements for feedback control were installed between the conducting shell and the vacuum vessel. The entire system includes approximately 1100 magnetic probes, 14 flux coils, 4×26×2 saddle sensors, and 16 Rogowski coils. Considering the large number of probes and limited space available in the vacuum vessel, the miniaturization of the probes and optimization of the probe distribution are necessary. In addition, accurate calibration and careful mounting of the probes are also required. The frequency response of the designed magnetic probes is up to 200 kHz, and the resolution is 1 G. The EDS, being spherical and of high precision, is one of the most basic and effective diagnostic tools of the KTX and meets the demands imposed by requirements on basic machine operating information and future studies.

The eddy current probe array for Keda Torus eXperiment.

In a reversed field pinch device, the conductive shell is placed as close as possible to the plasma so as to balance the plasma during discharge. Plasma instabilities such as the resistive wall mode and certain tearing modes, which restrain the plasma high parameter operation, respond closely with conditions in the wall, in essence the eddy current present. Also, the effect of eddy currents induced by the external coils cannot be ignored when active control is applied to control instabilities. One diagnostic tool, an eddy current probe array, detects the eddy current in the composite shell. Magnetic probes measuring differences between the inner and outer magnetic fields enable estimates of the amplitude and angle of these eddy currents. Along with measurements of currents through the copper bolts connecting the poloidal shield copper shells, we can obtain the eddy currents over the entire shell. Magnetic field and eddy current resolutions approach 2 G and 6 A, respectively. Additionally, the vortex electric field can be obtained by eddy current probes. As the conductivity of the composite shell is high, the eddy current probe array is very sensitive to the electric field and has a resolution of 0.2 mV/cm. In a bench test experiment using a 1/4 vacuum vessel, measurements of the induced eddy currents are compared with simulation results based on a 3D electromagnetic model. The preliminary data of the eddy currents have been detected during discharges in a Keda Torus eXperiment device. The typical value of toroidal and poloidal eddy currents across the magnetic probe coverage rectangular area could reach 3.0 kA and 1.3 kA, respectively.

Generation of volatile compounds in litchi wine during winemaking and short-term bottle storage.

Evolution of volatile components during litchi (Litchi chinensis Sonn.) winemaking was monitored, and aroma profiles of litchi wines bottle aged for 5 months at ambient temperature (25-28 °C) and low temperature (8-10 °C) were compared via headspace solid phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS). The majority of terpenoids deriving from litchi juice decreased, even disappeared along with alcoholic fermentation, while terpenol oxides, ethers, and acetates came into being and increased. Ethyl octanote, isoamyl acetate, ethyl hexanoate, ethyl butanoate, cis-rose oxide, and trans-rose oxide had the highest odor activity values (OAVs) in young litchi wines. Six aromatic series were obtained by grouping OAVs of odor-active compounds with similar odor descriptions to establish the aroma profile for young litchi wines, and floral and fruity attributes were two major aroma series. Compared to ambient temperature when bottle aging, lower temperature benefited key aroma retention and expectantly extended the shelf life of young litchi wines.