Anti-CD47/PD-L1 immunotherapies aiming to enhance antitumor immunity are being intensively investigated and show promising results in cancer therapy; however, not all patients treated with these new drugs respond. Thus, developing new immunotherapy agents or combination treatments to enhance the efficacy of immunotherapy is an urgent challenge. Here, we found that LSD1 knockdown directly downregulated the expression of CD47 and PD-L1 through upregulating H3K4me2 levels in the CD47 and CD274 promoter regions. In addition, the LSD1/wild-type p53/miR-34a signaling axis was also involved in the regulation of CD47/PD-L1 expression by targeting the 3′ untranslated regions (3′UTRs) of CD47/PD-L1. Further, the results showed that an LSD1 inhibitor (ORY-1001) combined with anti-CD47/PD-L1 monoclonal antibodies inhibited tumor growth in an established subcutaneous xenograft model more effectively than a single blockade strategy. Collectively, these findings indicate that LSD1 inhibition enhances the therapeutic efficacy of PD-L1/CD47 blockade by reducing CD47 and PD-L1 expression in cervical cancer.

Background: The activation of succinate receptor 1 (SUCNR1) by extracellular succinate has been found to regulate immune cell function. However, the clinical significance of SUCNR1 in ovarian cancer and its correlation with tumor-infiltrating lymphocytes remain unclear. Methods: The genetic alteration and expression patterns of SUCNR1 were analyzed by using cBioPortal and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier Plotter was used to assess the prognostic value of SUCNR1 in patients with ovarian cancer. The correlations between SUCNR1 expression and immune infiltration, gene markers of immune cells, cytokines, chemokines, or T cell exhaustion were explored by using TIMER and TISIDB platforms. We also performed Gene Set Enrichment Analysis (GSEA) to reveal biological function of SUCNR1 in ovarian cancer. Results: The expression of SUCNR1 was closely related to tumor infiltrating lymphocytes, multiple gene markers of immune cells, and T cell exhaustion in ovarian cancer. The expression of SUCNR1 was also associated with the expression of cytokine- or chemokine-related genes. Moreover, GSEA revealed that various immune-related pathways might be regulated by SUCNR1. In addition, we found that SUCNR1 was amplified in ovarian cancer, and the high expression of SUCNR1 predicted worse progression-free survival (p = 0.0073, HR = 1.49, 95% CI = 1.11–2). Conclusion: These results highlight the role of SUCNR1 in regulating tumor immunity in ovarian cancer.

Background: An organized cervical cancer screening program is an effective method to prevent and control cervical cancer. This study aims to find barriers and facilitators in the implementation process of National Cervical Cancer Screening Program in Rural Areas (NACCSPRA) in China through program evaluation, and thus propose suggestions for optimization of the program.Methods: Through stratified sampling, 8 provinces (autonomous cities/districts) in eastern, southern, western, northern, and central China were selected for evaluation of NACCSPRA based on the RE-AIM framework. We obtained 15 program providers' experience and perspectives through semi-structured interviews. The data was analyzed using a combination of deductive and inductive analysis methods.Results: The study found that NACCSPRA mainly serves women with rural household registration or urban minimum living guarantee. Population mobility and certain demographic characteristics such as low education and poor health awareness are common participation barriers, while program publicity acts as a facilitator. A screening program's direct benefit is to promote early detection and treatment of cervical cancer, and its perceived indirect effect is to raise people's health awareness. The proportion of regions adopting the project is relatively high, and factors affecting employees' participation are screening workload, working environment, welfare benefits, degree of preference for grassroots work, and whether the project is included in the performance appraisal; In terms of implementation, there are disparities in screening methods, network informatization levels, and capital investment in various regions. Poor development of screening information system and insufficient screening funds are significant barriers to improvement of project implementation. In contrast, the overall implementation of follow-up is better; related policies issued by the local government and financial subsidies for poor women ensure the maintenance of the project.Conclusion: Shortage of funds is an important problem faced by current screening project, which negatively influences upgrade of cervical cancer prevention strategy, implementors' working environment, and impedes improvement of information network. In addition, defects in population coverage, especially in mobile population also deserves attention. The study found barriers and facilitators of NACCSPRA perceived by project providers and provided a theoretical foundation for project optimization.

Background: Sulforaphane (SFN) is one kind of phytochemical anticancer drug. It inhibits cancer cell proliferation and promotes cell apoptosis while the mechanism behind is still uncertain. We aimed to explore its downstream target and the radiotherapy sensitization mechanism in cervical cancer. Methods: We treated established cervical cancer cells line (SiHa, HeLa, C33A) with SFN followed by irradiation, and explored its survival, apoptosis, and DNA damage repair in vitro and validated the radiosensitivity of SFN treatment in vivo. We conducted mRNA sequencing to identify differentially expressed mRNAs after SFN treatment. We further investigated SFN downstream target and its involvement in DNA damage repair under irradiation. Results: We found that SFN inhibited the survival of cervical cancer cells under radiotherapy treatment in vitro and prolonged the survival period after radiotherapy in the mouse tumorigenic model. SFN increased the protein expression of LATS2 and promoted apoptosis of cervical cancer cells. Overexpressed LATS2 decreased the cellular survival rate of cervical cancer cells. Additionally, SFN treatment and LATS2 overexpression prevented MDC1 and Rad51 from accumulating in the nucleus in cervical cancer cells after being exposed to ionized radiation. LATS2 loss intervened with SFN-alleviated RAD51 and MDC1 nucleus accumulation and resumed the repairment of DNA damage. Conclusion: We identified SFN as cervical cancer cells radiotherapy sensitizer and LATS2 served as a downstream target of SFN treatment. SFN treatment resulted in the inhibition of the homologous recombination (HR) pathway, and LATS2 has an indispensable contribution to this SFN-facilitated radiotherapy sensitization.

As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer. A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed. Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P < 0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively. In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.

Objective: This study aims to compare the results of cervical cancer screening in Shanghai General Hospital before and after the COVID-19 epidemic, and analyze the current status and related influencing factors of precervical cancer screening in our hospital under the COVID-19 pandemic. Methods: The data of 13,748 women of cervical precancer screening with HPV in Shanghai General Hospital were selected.The data included human papillomavirus (HPV), thin-layer liquid-based cytology test (TCT), colposcopy and cervical biopsy, and pathological diagnosis results after trachelectomy in 2019 and 2020, and were analyzed and compared. Results:The detection rates of precancerous lesions and cervical cancer were 2.9061/10,000 and 29.26/10,000 respectively. There was a significant difference in the rate of comparison (χ² = 30.361, P = 0.000; χ² = 7.682, P = 0.006);(2) Missing detection rate: In 2020, other positive subtypes other than HPV 16 and 18 who need TCT, the colposcopy, and the histopathological examination missing detection rate were higher than those in 2019 (P < 0.05);(3) Abnormal rate of examination: the abnormal rate of HPV, TCT, and histopathology in 2020 was higher than those in 2019 (P < 0.05);(4) Histopathological analysis: The detection rate of high-grade lesions and invasive cancer in 2020 was higher than those in 2019, and the detection rate of low-grade lesions was lower than that in 2019 (P < 0.05); Conclusion: Health authorities should formulate intervention measures to cope with the safe and timely implementation of cervical cancer screening and subsequent follow-up management during public health emergency.