Introduction: We performed a meta-analysis and an experimental validation to investigate the association between tumor infiltrating lymphocytes (TILs) and the outcome of gastric cancer (GC) patients to provide prognostic indicators for clinical practice. Material and methods: The relative literature of TILs in tumor tissue from patients with gastric cancer was searched from PubMed, Embase, NIH databases, from April 2000 to 31 December 2016. Studies on the prognostic value of TILs as CD3+, CD4+, CD8+, GrB+, and FOXP3+ lymphocytes for GC were retrieved, and also the related references were traced as supplements. Independent screening documents, extracting information and evaluating quality were implemented independently by 2 evaluators according to the inclusion and exclusion criteria, which were then analyzed by meta-analysis using STATA version 12.0 software. Results: The results indicated that high levels of intratumoral CD8+, CD3+ and CD4+ T cell infiltration were associated with better overall survival(OS) in gastric cancer patients, while high density of intratumoral FOXP3+ T cells was not closely associated with a worse outcome. Additionally, in our study, higher density of granzyme B+ (GrB+) T cell infiltration indicated an optimistic prognosis, and infiltration of a larger number of general TILs also suggested a favorable prognosis by log-rank test analysis. Conclusions: This meta-analysis clarified that high levels of CD8+, CD3+, and CD4+ T cell infiltration in tumor tissue showed better OS in GC patients, whereas high density of FOXP3+ T cell infiltration may not be recognized as a negative prognostic factor. These results may provide some useful prognostic indicators for clinical application in gastric cancer.

No abstract

No abstract

Objectives To evaluate the correlation between tumor-infiltrating lymphocytes (TILs) and the viral load of high-risk human papillomavirus (HR-HPV) in cervical cancer patients. Methods A total of 62 cervical cancer patients were recruited during 1993-1994 and assigned into four groups treated with radiotherapy alone or radiotherapy combined with chemotherapy and/or thermotherapy. Ki67+ tumor cells, CD4+, CD8+, FoxP3+, OX40+ and granzyme B+ TILs were detected by immunohistochemistry. The viral load of HR-HPV in biopsy tissues before therapy was detected by in situ hybridization. Results The patients with high HPV viral load showed a significantly lower 15-year survival rate and an advanced International Federation of Gynecology and Obstetrics (FIGO) stage and increased recurrence rate. The distribution of Ki67+ tumor cells, FoxP3+ TILs, and CD8+/FoxP3+ ratio was obviously different between low and high HPV viral load groups. A worse clinical outcome was also implicated with increased HPV viral load tested by Cox regression analysis. Conclusions Patients with increased HR-HPV viral load tend to be resistant to therapy with decreased immune surveillance in the immune microenvironment. Thus, HR-HPV viral load would influence the local immune microenvironment, and then further affect the survival of cervical cancer patients.

No abstract

No abstract

Background: : A major challenge in cervical cancer radiotherapy is to tailor the radiation doses efficiently to both eliminate malignant cells and to reduce the side effects to normal tissue. Oncolytic adenoviral drug H101 is recently tested and approved for topical adjuvant treatment of several malignancies. Objective: This study is to evaluate the potential neoadjuvant radiotherapy benefits of H101 by testing the inhibitory function of H101 combined with radiation in different cervical cancer cells. Methods: Human cervical cancer cells C33a, SiHa, CaSki, and Hela were treated with varying concentrations of H101 alone or combined with radiation (2Gy or 4Gy). Cell viability and apoptosis were measured at indicated time intervals. HPV16 E6 and cellular p53 mRNA expression alteration were measured by qRT-PCR. RNA scope in-situ detect HPV E6 status. P53 protein alteration are detected by Western blot. Results: Cell viability and apoptosis show the combination of a high dose of H101 (MOI=1000, 10000) with radiation yielded a synergistic anti-cancer effect in all tested cervical cancer cell lines (P<0.05), with the greatest effect achieved in HPV negative C33a cells (P<0.05). Low HPV16 viral load SiHa cell was more sensitive to combination therapy than high HPV16 viral load CaSki cell (P<0.05). The combined treatment could reduce HPV16 E6 expression and increase cellular P53 level compared to radiation alone in SiHa and CaSki (P<0.05). Conclusions: Oncolytic adenoviral H101 effectively enhances the antitumor efficacy of radiation in cervical cancer cells and may serve as a novel combination therapy for cervical cancer.

No abstract