T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8+ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models. 相似文献
The nucleation efficiency (NE) of stereocomplex crystallites (SCs) formed in asymmetric poly(L-lactide)/poly(D-lactide) (PLLA/PDLA) blends is generally unsatisfactory because the competition between stereocomplexation and chain mixing involved in the melt-mixing process can cause low formation efficiency and even severe aggregation of SCs. Herein, it is attempted to achieve high-efficient formation of finely dispersed SCs particles by designing a unique melt-mixing procedure, where the mixing of PLLA with 0.75 wt% PDLA is first performed at elevated temperatures (far above the melting temperature of SCs) to allow the homogeneous mixing of PLLA/PDLA chains and then at a low temperature (slightly above that of homocrystallites) to permit the full stereocomplexation of the premixed chains. It is found that the SCs formed in the blends exhibit unexpectedly low NEs (e.g., 54.5%), much inferior to that (73.6%) in the counterpart without undergoing premixing. This is because the introduction of premixing leads to a remarkable deterioration in the amount of SCs particles formed, despite decreased particle size, highlighting that the direct mixing at low temperatures of 170–180 °C (about 20–30 °C lower than that used in common melt-processing of PLA) is more effective for the construction of SCs with superior NE. The mechanisms for these striking findings are discussed. 相似文献
Comparative experiments are performed in friction stir welding (FSW) of dissimilar Al/Mg alloys with and without assistance of ultrasonic vibration. Metallographic characterization of the welds at transverse cross sections reveals that ultrasonic vibration induces differences in plastic material flow in two conditions. In FSW, the plastic material in the peripheral area of shoulder-affected zone (SAZ) tends to flow downward because of the weakening of the driving force of the shoulder, and a plastic material insulation layer is formed at the SAZ edge. When ultrasonic vibration is exerted, the stirred zone is divided into the inner and outer shear layers, the downward material flow trend of the inner shear layer disappears and tends to flow upward, and the onion-ring structure caused by the swirl motion is avoided in the pin-affected zone. By improving the flow behavior of plastic materials in the stirred zone, ultrasonic vibration reduces the heat generation, accelerates the heat dissipation in nugget zone and changes the thermal cycles, thus inhibiting the formation of intermetallic compound layers.