A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy / 国际口腔科学杂志·英文版

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.

Study on the role of bone morphogenetic protein 4 in mediating acid and glycocholic acid induced Barrett′s esophagus / 中华消化杂志

Objective To investigate the mechanism of bone morphogenetic protein 4(BMP4) in the genesis of Barrett′s esophagus.Methods Human esophageal epithelial cell (HEEC) and MRC-5 were cultured.The effects of different concentration of BMP4 and different pH value of hydrochloric acid or glycocholic acid on the expression of caudal-related homeobox transcription factor 2(CDX2) in HEEC were detected by real time polymerase chain reaction.The effects of different pH value of hydrochloric acid or glycocholic acid on BMP4 expression in MRC-5 were also investigated.Independent sample t test was performed for statistical analysis.Results After HEEC stimulated by BMP4 at 0.1, 1.0, 10.0 and 100.0 ng/mL, the relative quantity expressions of CDX2 were 1.617±0.246, 2.489±0.455, 5.629±0.449 and 13.670±1.689, respectively, which were higher than those of control group (1.000±0.043, 1.029±0.094, 1.001±0.002 and 1.049±0.051, respectively), and the differences were statistically significant (t=2.47, 3.14, 10.31, 7.47;all P<0.05).After MRC-5 stimulated by acid at pH four or five, or glycocholic acid at pH four or five, the relative quantity expressions of BMP4 were 2.430±0.105, 2.394±0.145, 125.900±12.620 and 2.128±0.215, respectively, which were higher than those of control group(1.025±0.095, 0.999±0.007, 1.060±0.138 and 0.893±0.110,respectively), and the differences were statistically significant (t=9.94, 9.59, 9.89, 5.11;all P<0.01).Conclusion BMP4 can increase the expression of CDX2 in HEEC, which promote the genesis of Barrett′s esophagus.

Prostatic calculus caused by nanobacteria infection in SD rats / 中华泌尿外科杂志

Objective To reproduce an SD rat model of prostatic calculus by using nanobacteria (NB), and explore the role of NB in contributing to prostatitis and prostatic calculus. Methods Twenty adult male SD rats were randomized to the control group and 20 to the model group. Rat prostate infection models were reproduced by infusing 0. 2 ml (Concentration, 1 Mai unit) NB suspension transurethrally. 0.2 ml physiological saline was infused transurethrally in the rat control group. The rats were sacrificed 4 and 8 weeks later and prostatic pathology were viewed by hematoxylin and eosin (HE) staining. Lithogenesis was observed by scanning electron microscope (SEM) or Transmission electron microscopy (TEM). Re-isolation, culture and identification of nanobacteria were also done in rat prostatic tissues. Results Chronic inflammatory changes of prostates were shown in the model group at both 4 weeks and 8 weeks after infusing NB suspension. Prostatic calculi were detected by SEM and TEM at 8 weeks in the prostates of the rat model group (7/10). Neither chronic inflammatory changes nor prostatic calculus was found in the control group. NB was positive in the model group, but negative in the control group. Conclusions NB infection could cause chronic prostatitis and prostatic calculus in rats.