RESUMEN

Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, which ranks sixth in cancer incidence and third in mortality. Although great strides have been made in novel therapy for HCC, such as immunotherapy, the prognosis remains less than satisfactory. Increasing evidence demonstrates that the tumor immune microenvironment (TME) exerts a significant role in the evolution of HCC and has a non-negligible impact on the efficacy of HCC treatment. In the past two decades, the success in hematological malignancies made by chimeric antigen receptor-modified T (CAR-T) cell therapy leveraging it holds great promise for cancer treatment. However, in the face of a hostile TME in solid tumors like HCC, the efficacy of CAR-T cells will be greatly compromised. Here, we provide an overview of TME features in HCC, discuss recent advances and challenges of CAR-T immunotherapy in HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Receptores Quiméricos de Antígenos , Carcinoma Hepatocelular/terapia , Humanos , Inmunoterapia , Neoplasias Hepáticas/terapia , Linfocitos T , Microambiente Tumoral

RESUMEN

Objective To investigate the significance of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and ambulatory urodynamics monitoring (AUM) to find the cause of primary monosymptomatic nocturnal enuresis (PMNE) in children.Methods Thirty-seven children with PMNE (20 males and 17 females) were selected,with a mean age of (11.3 ±4.1) years old.A clinical management tool,3-day urination record,daytime BOLD-fMRI scan,conventional urodynamics (CUD) and AUM were performed respectively.Thirty-seven gender-age matched children(19 males,18 females) who would receive surgery treatment because of upper urinary tract disease and were confirmed to have no lower urinary tract dysfunction by CUD were enrolled as controls,with a mean age of (11.1 ± 2.9) years old,and 13 cases underwent BOLD-fMRI scanning.Results It was found that the ALFF value of the left middle frontal gyrus of PMNE was decreased and the ReHo value of the left superior occipital gyrus was increased compared with the control group by the resting BOLD-fMRI.The maximum voiding volume of PNME children was (303.11 ± 87.48) mL,the total urine volume at night was (568.65 ± 208.48) mL,and the nighttime bladder volume was (217.43 ± 81.53) mL.The incidence of maximum voiding volume reduction,nocturnal polyuria and decreased nocturnal bladder volume were 24.32％ and 56.76％,and 64.86％,respectively.However,AUM results showed that maximum detrusor pressure in the PMNE group was (39.22 ± 7.78) cmH2O (1 cmH2O =0.098 kPa),which was statistically significantly higher than that in CUD (32.22 ±9.00) cmH2O,and the difference was statistically significant (P ＜0.05).In PMNE group,29 cases (78.37％) had detrusor overactivity (DO),which was significantly higher than that in CUD group [16 cases (43.24％)],and the difference was statistically significant(t =-3.047,P =0.004).CUD and AUM were all detected in children with DO,the frequency of DO detected by AUM was significantly higher than that detected by CUD[(2.00 ±0.55 times/h) vs.(1.38 ±0.50) times/h,P ＜0.05],and the maximum amplitude of detrusor pressure when DO occurring was significantly higher in AUM than in CUD [(19.56 ± 6.01) cmH2O vs.(14.38 ± 3.07) cmH2O],and the differences were statistically significant (all P ＜ 0.05);however,there was no significant difference in bladder compliance detected by AUM or CUD (P ＞ 0.05).Conclusions The abnormal functions of the left middle frontal gyrus and left superior occipital gyrus,nighttime DO and the decrease of bladder capacity at night are considered to be key causes of enuresis in children with PMNE.AUM and resting state BOLD-fMRI evaluations are helpful in differentiating the pathogenesis of PMNE.