ABSTRACT
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.
Subject(s)
Humans , CD8-Positive T-Lymphocytes , Head and Neck Neoplasms/therapy , Immunotherapy/methods , Prognosis , Programmed Cell Death 1 Receptor , Squamous Cell Carcinoma of Head and Neck/therapy , Tumor Microenvironment , Tumor Necrosis Factor-alphaABSTRACT
Laparoscopic cholecystectomy is considered the gold standard for the treatment of symptomatic cholecystolithiasis and has become one of the typical representatives of minimally invasive surgery. This article briefly introduces the contraindication and indication for laparoscopic cholecystectomy, commonly used surgical procedures, and possible complications and related treatment methods, emphasizes the improvement of surgical procedure and the development of new equipment for cholecystectomy, and points out the current status, problems, and development trend of laparoscopic cholecystectomy, in order to provide a reference for better application of laparoscopic cholecystectomy in clinical practice.
ABSTRACT
BACKGROUND: Poor root canal filling or poor post-core crown restoration can cause microleakage between the implant material and the tooth, leading to secondary infection of the periapical tissue and affecting long-term effect of tooth restoration. OBJECTIVE: To analyze the microleakage in a glucose penetration model when post space preparation is performed with different timing and remaining lengths. METHODS: Eighty-six freshly extracted mandibular premolars from the Orthodontics Department of Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University were randomly divided into eight groups: positive control group (n=10) undertook root canal preparation; negative control group (n=10) undertook root canal preparation and filling but not post space preparation; A1, B1 and C1 groups (n=11 per group) were subjected to root canal filling immediately followed by post space preparation with the filling material of 4 mm, 5 mm, and 6 mm in length, respectively; A2, B2 and C2 groups were subjected to root canal filling and 1 week after filling, the three groups underwent post space preparation with the filling material of 4, 5 and 6 mm in length, respectively. At 48 hours after post space preparation, the integration of root canal wall and filling material was observed by scanning electron microscopy. The glucose microleakage model was used to detect the amount of glucose leaking from the crown to the root in each group. RESULTS AND CONCLUSION: (1) Under the scanning electron microscope, the fillings were most tightly bonded to the root canal wall in C1, while microcracks were most apparent in A2. (2) According to the measurement of glucose penetration model, A2 showed more microleakage than A1 (P < 0.05), B2 showed more microleakage than B1 (P < 0.05), and there was no statistically significant difference between C1 and C2 (P> 0.05). No significant difference was found among A1, B1 and C1 (P> 0.05), B2 showed no statistical difference in the microleakage from A2 and C2 (P> 0.05), but A2 showed more microleakage than C2 (P′ < 0.017). These results indicate that immediate post space preparation is superior to delayed preparation in reducing the microleakage. For immediate post space preparation, the remaining length of the filling material has no effect on the microleakage, but for delayed preparation, the filling material of at least 5 mm in length should be preserved.