T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to...T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma model.To achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of IRF4.GFP exhibited a more differentiated PD-1high cell phenotype.By administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted IRF4.GFP^(+)TILs and observed an accelerated tumor growth.To specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)models.Firstly,depleting IRF4.GFP^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor progression.Secondly,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ACT.Lastly,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor control.Therefore,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.展开更多
Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing not...Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.展开更多
基金The research received support from internal fund provided by the Houston Methodist Research Institute to W.C.
文摘T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma model.To achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of IRF4.GFP exhibited a more differentiated PD-1high cell phenotype.By administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted IRF4.GFP^(+)TILs and observed an accelerated tumor growth.To specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)models.Firstly,depleting IRF4.GFP^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor progression.Secondly,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ACT.Lastly,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor control.Therefore,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.
文摘Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.
