Background:The blockade of PD-1–PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1–PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1–PD-L1 pathway in CD8+ T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients.Methods:PD-1 expression on CD8+ T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8+ T cells were detected by intracellular staining.Results:PD-1 expression is markedly upregulated on CD8+ T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8+ T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1+ CD8+ T cells.Conclusions:Our findings suggest a suppressive effect of PD-1 on CD8+ T-cell function in tumours, but not in TFLNs.

Although HPV18 appeared to be less frequent among population-based samples of China, given the high prevalence of HPV 16 and 18 in high-grade squamous intraepithelial lesion (HSIL) or worse pap abnormalities, prophylactic HPV16/18 vaccines should substantially reduce the burden of cervical cancer in China.

Background: Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays a key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven to be a tumor-dependent circRNA. However, its role in non-small cell lung cancer (NSCLC) has been underreported. Methods:The expression patterns of circ-ZKSCAN1 were determined using qRT-PCR in NSCLC samples and cell lines. Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. The combination of circ-ZKSCAN1 and miR-330-5p in NSCLC cells was analyzed by RNA pull-down and luciferase reporter assay. We used the bioinformatics software circbank, CircInteractome, TargetScan and Miranda to predict circRNA-miRNA and miRNA-mRNA interactions.Results: Our results showed that circ-ZKSCAN1 was significantly up-regulated in NSCLC, closely related to malignant characteristics and poor prognosis, and clinically related to tumor size and clinical stage.Subsequent experiments showed that circ-ZKSCAN1 could inhibit the growth of NSCLC cells in vitro and in vivo. Importantly, circ-ZKSCAN1 can act as a sponge of carcinogenic miR-330-5p to increase the expression of FAM83A, resulting in the inhibition of MAPK signal transduction pathway, thus promoting the progress of NSCLC. Interestingly, the increase in FAM83A expression caused by circ-ZKSCAN1 overexpression could in turn promote the expression of circ-ZKSCAN1.Conclusions: Circ-ZKSCAN1 is a key positive regulator of NSCLC, and clarifies the potential molecular mechanism of the new circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop in promoting the progress of NSCLC.

BackgroundAdoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells’ ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain.MethodsA second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model.ResultsChimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour 51Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII expressing glioma cells.ConclusionsOur study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment.

Purpose To investigate the impact of the COVID-19 pandemic on patients with colorectal cancer undergoing elective surgery. Methods The medical records of patients with colorectal cancer who underwent elective surgery in our department during the COVID-19 pandemic (February 1 to May 31, 2020) were collected and analyzed. We compared the clinical data with colorectal cancer during the same 4-month period in 2018 and 2019. Results Sixty-seven patients with colorectal cancer underwent elective surgery during the COVID-19 pandemic. This was 66% of the number of patients that underwent the procedure during the same period in 2018 and 2019. During the COVID-19 pandemic, the proportion of patients without any digestive system symptoms decreased to 3% and severe clinical symptoms decreased by 20.9%. The proportion of right colon cancer decreased by 17.9%, while the proportion of rectal cancer increased by 52.2%, as compared with 2018 and 2019. The fraction of protective stoma was significantly higher than in 2018 (23.9% vs. 8.7%, p = 0.011). Compared with 2019, the average post-operative stay was significantly shorter than in 2018 (9.6 ± 3.7 vs. 12.1 ± 9.1, p = 0.015). Compared with 2019, the number of patients with perineural invasion (a feature of adverse prognosis) significantly increased ( p = 0.009). Conclusion During the COVID-19 pandemic, the number of patients undergoing elective surgery for colorectal cancer was reduced. However, the tumor stage of patients did not change substantially. We suggest that the clinical diagnosis and treatment of colorectal cancer should strictly comply with national and professional standards.

The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization.

Background: Nutritional status, systemic inflammation, and coagulation mechanism are closely related to tumor progression. Herein, we examined the role of fibrinogen-to-albumin ratio index (FARI) in the prognosis of gastrointestinal stromal tumors (GISTs) and developed a novel nomogram predicting recurrence-free survival (RFS). Methods: We retrospectively analyzed data from 357 GIST patients admitted at the gastrointestinal surgery of the Beijing Hospital from January 2008 to January 2018 and underwent curative resection. FARI was calculated as fibrinogen level (g/L) /albumin level (g/L). The cutoff point of FARI was set using the point with the largest Youden index on the receiver operating characteristic curve with the 5-years recurrence-free survival as an endpoint. We used the Kaplan-Meier approach and multivariable Cox regression model to study the impact of FARI on recurrence-free survival. Finally, we developed a nomogram based on tumor size, location, mitotic index, and FARI to predict RFS. The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with the National Institute of Health (NIH) risk classification system. Results: The ROC curve revealed that the best cutoff point of the FARI was set as 0.08. The patients were classified into the FARI-high (≥0.08) and FARI-low (<0.08) groups. FARI was significantly associated with age, size of the tumor, NIH risk category, and Mitotic Index (all P < 0.05). FARI was weakly associated with NLR and PLR. FARI and PNI had a weak negative association. Multivariate analysis showed that the NIH risk category and FARI were independent prognostic predictors for worse outcomes concerning RFS in GIST patients. In the high-risk subgroup, patients with low FARI also had a more prolonged RFS than patients with high FARI (P <0.05). The nomogram had a concordance probability of 0.802 (SE 0.025). Nomogram predictions were well-calibrated. Concordance probabilities of the nomogram were better than NIH risk classification system [0.802 [0.025] vs. 0.737 [0.024], p < 0.01].

Background. The use of the surgical robot for standard lobectomy has widely spread worldwide. However there are relatively few studies of robotic bronchial sleeve lobectomy for central lung tumors.Methods. We retrospectively evaluated 67 consecutive patients who underwent robotic bronchial sleeve lobectomy, a procedure without pulmonary vessel end-to-end anastomosis, performed by a single surgeon between October 2014 and March 2018. A half-continuous suture technique with two Prolene (Ethicon, Inc, Somerville, NJ) sutures for bronchial anastomosis was applied. The operative techniques and outcomes were analyzed.Results. Complete resection was achieved in all patients undergoing different types of robotic bronchial sleeve lobectomy. There were no conversions to thoracotomy. The mean total surgical duration was 166.5 minutes (range, 78-286), total bronchial anastomosis time was 20.8 minutes (range, 10-44), estimated blood loss was 98.8 mL (range, 20-300), and postoperative hospital stay was 6.8 days (range, 4-13). No patient died within 90 days after surgery. The postoperative morbidity rate was 20.9%. Multivariate analysis showed that preoperative comorbidity, older age, and surgeon's early experience were risk factors for postoperative morbidity.Conclusions. Robotic bronchial sleeve lobectomy and the novel anastomotic technique are both feasible and safe for carefully selected patients.