Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was t...Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25（OH）D], total testosterone （TT）, and free testosterone （FT） in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7± 7.9 years, and the mean serum 25（OH）D, TT and FT levels were 21.23 ± 7.9 ng m1-1, 4.70 ±1.6 ng m1-1, and 8.12± 3.3 pg m1-1, respectively. In the multiple linear regression model, 25（OH）D showed positive association with TT （β =0.137, P〈 0.001） and FT （p =0.103, P= 0.008）. 25（OH） D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25（OH）D 〈 20 ng m1-1] was associated with an increased risk of deficiencies of TT （〈2.30 ng ml-1） （odds ratio [OR]： 2.65; 95% confidence interval [CI]. 1.21-5.78, P = 0.014） and FT （〈6.50 pg ml-1） （OR： 1.44; 95% Ch 1.01-2.06 P = 0.048） after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25（OH）D and testosterone, which showed similar seasonal variation in Korean men.展开更多
The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy.However,the adverse side effects associated with agonist antibodies have hindered their clinical deve...The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy.However,the adverse side effects associated with agonist antibodies have hindered their clinical development.Here,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs.We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction.However,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γaxis.This was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T cells.Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.展开更多
文摘Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25（OH）D], total testosterone （TT）, and free testosterone （FT） in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7± 7.9 years, and the mean serum 25（OH）D, TT and FT levels were 21.23 ± 7.9 ng m1-1, 4.70 ±1.6 ng m1-1, and 8.12± 3.3 pg m1-1, respectively. In the multiple linear regression model, 25（OH）D showed positive association with TT （β =0.137, P〈 0.001） and FT （p =0.103, P= 0.008）. 25（OH） D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25（OH）D 〈 20 ng m1-1] was associated with an increased risk of deficiencies of TT （〈2.30 ng ml-1） （odds ratio [OR]： 2.65; 95% confidence interval [CI]. 1.21-5.78, P = 0.014） and FT （〈6.50 pg ml-1） （OR： 1.44; 95% Ch 1.01-2.06 P = 0.048） after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25（OH）D and testosterone, which showed similar seasonal variation in Korean men.
基金This study was supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(2018R1A6A3A01011692[SHK]from MOE and 2019R1C1C1008999[CH]from MSIT)the National Cancer Center of Korea(NCC-1810102/191050/1911261[BKC]and NCC-2010190[CH]).
文摘The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy.However,the adverse side effects associated with agonist antibodies have hindered their clinical development.Here,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs.We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction.However,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γaxis.This was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T cells.Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.
