浅谈癌症免疫治疗中的新型免疫细胞接合器

免疫疗法是治疗癌症的一种革命性方法,包括基于细胞的疗法、疫苗、检查点抑制剂和靶向抗体,以及涉及免疫细胞接合器的最新方法。免疫细胞接合器是一种基于生物工程抗体的分子,旨在将免疫细胞重定向至肿瘤。大多数免疫细胞接合器是具有多个臂的抗体,通过靶向肿瘤抗原和效应细胞表面分子来桥接肿瘤细胞和效应细胞。效应细胞分子必须触发激活免疫效应细胞杀伤机制的信号通路。因此,这些分子的作用模式是在肿瘤细胞和免疫细胞之间形成免疫突触。第一代双特异性免疫细胞接合器被设计成靶向T细胞上CD3和白血病B细胞上的肿瘤抗原如CD19。这些药物在治疗血液系统恶性肿瘤患者方面已显示出良好的疗效,但仍存在许多挑战。特别是,细胞因子释放综合征(CRS)和免疫效应细胞相关的神经毒性,以及治疗后复发和实体瘤疗效不佳,都是严重的挑战。目前,人们正在努力提高T细胞接合器的安全性和有效性,包括开发对CD3具有较低亲和力的分子,靶向共刺激T细胞分子,并且可以在肿瘤微环境中被条件激活。此外,还正在探索靶向具有内在肿瘤细胞杀伤能力的其他类型的免疫效应细胞,如γδT细胞、自然杀伤(NK)细胞和髓系细胞。

Representation of the ENSO Combination Mode and its Asymmetric SST Response in Different Resolutions of HadGEM3

Previous studies have revealed a combination mode （C-mode） occurring in the Indo-Pacific region, arising from nonlinear interactions between ENSO and the western Pacific warm pool annual cycle. This paper evaluates the simulation of this C-mode and its asymmetric SST response in HadGEM3 and its resolution sensitivity using three sets of simulations at horizontal resolutions of N96, N216 and N512. The results show that HadGEM3 can capture well the spatial pattern of the C-mode associated surface wind anomalies, as well as the asymmetric response of SST in the tropical Pacific, but it strongly overestimates the explained variability of the C-mode compared to the ENSO mode. The model with the three resolutions is able to reproduce the distinct spectral peaks of the C-mode at the near annual combination frequencies, but the performance in simulating the longer periods is not satisfactory, presumably due to the unrealistic simulation of the ENSO mode. Increasing the horizontal resolution can improve the consistency between atmospheric and oceanic representations of the C-mode, but not necessarily enhance the accuracy of C-mode simulation compared with observation.

Will the Historic Southeasterly Wind over the Equatorial Pacific in March 2022 Trigger a Third-year La Niña Event?

Based on the updates of the Climate Prediction Center and International Research Institute for Climate and Society(CPC/IRI)and the China Multi-Model Ensemble(CMME)El Niño-Southern Oscillation(ENSO)Outlook issued in April 2022,La Niña is favored to continue through the boreal summer and fall,indicating a high possibility of a three-year La Niña(2020-23).It would be the first three-year La Niña since the 1998-2001 event,which is the only observed three-year La Niña event since 1980.By examining the status of air-sea fields over the tropical Pacific in March 2022,it can be seen that while the thermocline depths were near average,the southeasterly wind stress was at its strongest since 1980.Here,based on a quaternary linear regression model that includes various relevant air-sea variables over the equatorial Pacific in March,we argue that the historic southeasterly winds over the equatorial Pacific are favorable for the emergence of the third-year La Niña,and both the anomalous easterly and southerly wind stress components are important and contribute~50%of the third-year La Niña growth,respectively.Additionally,the possible global climate impacts of this event are discussed.

Estimation of ground heat flux and its impact on the surface energy budget for a semi-arid grassland

Three approaches, i.e., the harmonic analysis （HA） technique, the thermal diffusion equation and correction （TDEC） method, and the calorimetric method used to estimate ground heat flux, are evaluated by using observations from the Semi-Arid Climate and Environment Observatory of Lanzhou University （SACOL） in July, 2008. The calorimetric method, which involves soil heat flux measurement with an HFP01SC self-calibrating heat flux plate buried at a depth of 5 cm and heat storage in the soil between the plate and the surface, is here called the ITHP approach. The results show good linear relationships between the soil heat fluxes measured with the HFP01SC heat flux plate and those calculated with the HA technique and the TDEC method, respectively, at a depth of 5 cm. The soil heat fluxes calculated with the latter two methods well follow the phase measured with the HFP01SC heat flux plate. The magnitudes of the soil heat flux calculated with the HA technique and the TDEC method are close to each other, and they are about 2 percent and 6 percent larger than the measured soil heat flux, respectively, which mainly occur during the nighttime. Moreover, the ground heat fluxes calculated with the TDEC method and the HA technique are highly correlated with each other （R2= 0.97）, and their difference is only about 1 percent. The TDEC-calculated ground heat flux also has a good linear relationship with the ITttP-calculated ground heat flux （R2 = 0.99）, but their difference is larger （about 9 percent）. Furthermore, compared to the HFP01SC direct measurements at a depth of 5 cm, the ground heat flux calculated with the HA technique, the TDEC method, and the ITHP approach can improve the surface energy budget closure by about 6 percent, 7 percent, and 6 percent at SACOL site, respectively. Therefore, the contribution of ground heat flux to the surface energy budget is very important for the semi-arid grassland over the Loess Plateau in China. Using turbulent heat fluxes with common corrections, soil heat storage between the surface and the heat flux plate can improve the surface energy budget closure by about 6 to 7 percent, resulting in a closure of 82 to 83 percent at the SACOL site.

Spatiotemporal distribution and decadal change of the monthly temperature predictability limit in China

Based on the nonlinear Lyapunov exponent and nonlinear error growth dynamics, the spatiotemporal distribution and decadal change of the monthly temperature predictability limit(MTPL) in China is quantitatively analyzed. Data used are daily temperature of 518 stations from 1960 to 2011 in China. The results are summarized as follows:(1) The spatial distribution of MTPL varies regionally. MTPL is higher in most areas of Northeast China, southwest Yunnan Province, and the eastern part of Northwest China. MTPL is lower in the middle and lower reaches of the Yangtze River and Huang-huai Basin.(2)The spatial distribution of MTPL varies distinctly with seasons. MTPL is higher in boreal summer than in boreal winter.(3) MTPL has had distinct decadal changes in China, with increase since the 1970 s and decrease since2000. Especially in the northeast part of the country, MTPL has significantly increased since 1986. Decadal change of MTPL in Northwest China, Northeast China and the Huang-huai Basin may have a close relationship with the persistence of temperature anomaly. Since the beginning of the 21 st century, MTPL has decreased slowly in most of the country, except for the south. The research provides a scientific foundation to understand the mechanism of monthly temperature anomalies and an important reference for improvement of monthly temperature prediction.