The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present stu...The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present study,we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer(HNSCC)by multiplex immunohistochemistry(mIHC)to investigate two subsets of Tex,CD8+PD1+TCF1+progenitor exhausted T cells(TCF1+Texprog)and CD8+PD1+TCF1−terminally exhausted T cells(TCF1−Texterm).Moreover,fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells(Tregs)in the tumor immune microenvironment(TIME).mIHC and flow cytometry analysis showed that TCF1−Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients.TCF1+Texprog produced abundant TNFα,while TCF1−Texterm expressed higher levels of CD103,TIM-3,CTLA-4,and TIGIT.TCF1−Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+phenotype;and were associated with better overall survival and recurrence-free survival.The results also indicated that larger proportions of TCF1−Texterm were accompanied by an increase in the proportion of Tregs.Therefore,it was concluded that TCF1−Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival.A high proportion of TCF1−Texterm was associated with greater Treg abundance.展开更多
Fruit specific promoter (2A12) from Lycopersi-com esculentum and cDNA of isopentenyl-transferase (ipt) from Ti plasmid of Agrobacterium tumerfaciens C58 were cloned by PCR procedure respectively. Two plant expression ...Fruit specific promoter (2A12) from Lycopersi-com esculentum and cDNA of isopentenyl-transferase (ipt) from Ti plasmid of Agrobacterium tumerfaciens C58 were cloned by PCR procedure respectively. Two plant expression vectors with 2A12/gus or 2A12/ipt were respectively constructed. These two chimeric genes were transferred into tomato by Agrobacterium mediated procedure. The results of Southern hybridization showed that the fusion genes had been integrated into tomatoes. The result of gus histochemi-cal staining showed that 2A12 had high fruit specific expressive capability in transgenic tomato. The ipt expression resulted in accumulation of high level of cytokinins (CTKs) in fruit lead to developmental changes in fruits and seeds. The fruit of ipt transformed tomato had the hyperplastic placenta with very few seeds or even seedless. The shelf life of transgenic fruits elongated for 1-2 weeks. The ratio of fruit set, the dry weight of fruit and the crude protein content in fruit were increased, while展开更多
From the insurer＇s point of view, this paper studies the optimal investment and proportional reinsurance in the Sparre Andersen model. Under the criterion of maximizing the adjustment coefficient, the authors obtain ...From the insurer＇s point of view, this paper studies the optimal investment and proportional reinsurance in the Sparre Andersen model. Under the criterion of maximizing the adjustment coefficient, the authors obtain the closed form expressions of the optimal strategy and the maximal adjustment coefficient, and derive the explicit expression of the ruin probability or its lower bound when the claim sizes are exponentially distributed. Some numerical examples are presented, which show the impact of model parameters on the optimal values. It can also be seen that the optimal strategy to maximize the adjustment coefficient is sometimes equivalent to those which minimize the ruin probability.展开更多
基金supported by the National Natural Science Foundations of China (Nos. 81972532, 81991500, 82101017, 81902778, and 81500864)Guangdong Basic and Applied Basic Research Foundation (2020A1515110741)
文摘The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy efficacy.However,few studies have explored exhausted T cell subpopulations in human cancers.In the present study,we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer(HNSCC)by multiplex immunohistochemistry(mIHC)to investigate two subsets of Tex,CD8+PD1+TCF1+progenitor exhausted T cells(TCF1+Texprog)and CD8+PD1+TCF1−terminally exhausted T cells(TCF1−Texterm).Moreover,fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells(Tregs)in the tumor immune microenvironment(TIME).mIHC and flow cytometry analysis showed that TCF1−Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients.TCF1+Texprog produced abundant TNFα,while TCF1−Texterm expressed higher levels of CD103,TIM-3,CTLA-4,and TIGIT.TCF1−Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+phenotype;and were associated with better overall survival and recurrence-free survival.The results also indicated that larger proportions of TCF1−Texterm were accompanied by an increase in the proportion of Tregs.Therefore,it was concluded that TCF1−Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival.A high proportion of TCF1−Texterm was associated with greater Treg abundance.
基金This work was supported by the Foundation for Ph. D. Student Research Station of the Ministry of Education.
文摘Fruit specific promoter (2A12) from Lycopersi-com esculentum and cDNA of isopentenyl-transferase (ipt) from Ti plasmid of Agrobacterium tumerfaciens C58 were cloned by PCR procedure respectively. Two plant expression vectors with 2A12/gus or 2A12/ipt were respectively constructed. These two chimeric genes were transferred into tomato by Agrobacterium mediated procedure. The results of Southern hybridization showed that the fusion genes had been integrated into tomatoes. The result of gus histochemi-cal staining showed that 2A12 had high fruit specific expressive capability in transgenic tomato. The ipt expression resulted in accumulation of high level of cytokinins (CTKs) in fruit lead to developmental changes in fruits and seeds. The fruit of ipt transformed tomato had the hyperplastic placenta with very few seeds or even seedless. The shelf life of transgenic fruits elongated for 1-2 weeks. The ratio of fruit set, the dry weight of fruit and the crude protein content in fruit were increased, while
基金supported by the National Natural Science Foundation of China under Grant No.11101215the Natural Science Foundation of the Jiangsu Higher Education Institutions of China under Grant No. 09KJB110004
文摘From the insurer＇s point of view, this paper studies the optimal investment and proportional reinsurance in the Sparre Andersen model. Under the criterion of maximizing the adjustment coefficient, the authors obtain the closed form expressions of the optimal strategy and the maximal adjustment coefficient, and derive the explicit expression of the ruin probability or its lower bound when the claim sizes are exponentially distributed. Some numerical examples are presented, which show the impact of model parameters on the optimal values. It can also be seen that the optimal strategy to maximize the adjustment coefficient is sometimes equivalent to those which minimize the ruin probability.
