Background: In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses. Methods: To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme^{−/ −} ID8 tumor cells into C57BL/6 mice. Results: Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1–caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model. Conclusions: PARPis induce a specific type of ICD called pyroptosis via TNF–caspase 8–GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions. Trial registration number: NCT04507841.

Background Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57–3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33–17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27–11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02–1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57–1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61–1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30–2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10–2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42–1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42–105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.

Objective: Accessibility to quality healthcare, histopathology of tumor, tumor stage and geographical location influence survival rates. Comprehending the bases of these differences in cervical cancer survival rate, as well as the variables linked to poor prognosis, is critical to improving survival. We aimed to perform the first thorough meta-analysis and systematic review of cervical cancer survival times in Africa based on race, histopathology, geographical location and age.Methods and materials: Major electronic databases were searched for articles published about cervical cancer survival rate in Africa. The eligible studies involved studies which reported 1-year, 3-year or 5-year overall survival (OS), disease-free survival (DFS) and/or locoregional recurrence (LRR) rate of cervical cancer patients living in Africa. Two reviewers independently chose the studies and evaluated the quality of the selected publications, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P). We used random effects analysis to pooled the survival rate across studies and heterogeneity was explored via sub-group and meta-regression analyses. A leave-one-out sensitivity analysis was undertaken, as well as the reporting bias assessment. Our findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P).Results: A total of 16,122 women with cervical cancer were covered in the 45 articles (59 studies), with research sample sizes ranging from 22 to 1,059 (median = 187.5). The five-year overall survival (OS) rate was 40.9% (95% CI: 35.5–46.5%). The five-year OS rate ranged from 3.9% (95% CI: 1.9–8.0%) in Malawi to as high as 76.1% (95% CI: 66.3–83.7%) in Ghana. The five-year disease-free survival rate was 66.2% (95% CI: 44.2–82.8%) while the five-year locoregional rate survival was 57.0% (95% CI: 41.4–88.7%).Conclusion: To enhance cervical cancer survival, geographical and racial group health promotion measures, as well as prospective genetic investigations, are critically required.

Purpose: Recent studies have validated microRNAs (miRNAs) as a diagnostic biomarker for haematological cancers. This study aimed to estimate the overall diagnostic accuracy of circulating miRNAs in haematological malignancies. Materials and Methods: Multiple databases (Google Scholar, PubMed, EMBASE, Cochrane Library,) were searched until 19^th, August 2017. Results: The meta-analysis included 50 studies from 20 publications. The diagnostic accuracy was assessed by pooled specificity, sensitivity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve area (AUC) by random effect model. We used QUADAS (Quality Assessment for diagnostic accuracy studies) to evaluate the quality of the included studies. To perform the meta-analysis, we used Meta-Disk 1.4, Revman 5.3 and Stata 12.0 software. High diagnostic accuracy was demonstrated, with a sensitivity of 0.81, a specificity of 0.85, a PLR of 5.28, an NLR of 0.22, a DOR of 30.39, and an AUC of 0.91. Subgroup analyses showed better outcomes for the African population, combined miRNAs and leukaemia patients compared with other subgroups. Conclusion: Our results indicated that circulating miRNAs especially combined miRNA can be used as a diagnostic marker in haematological cancers.

Background: Hypomethylating agents (HMAs), such as decitabine (DAC), are currently used as first-line therapy for patients with high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) not eligible for standard chemotherapies. Exacerbation of thrombocytopenia is one of the prevalent complications after HMA treatment. Eltrombopag (EP), an oral thrombopoietin receptor agonist, can efficiently stimulate megakaryopoiesis and elevate platelet counts in MDS/AML patients. However, the significance of combining EP with HMAs in patients with high-risk MDS/AML has not been determined. Purpose: To explore the impacts and mechanisms of EP and/or DAC on leukemia cell growth and to explore whether EP exhibits antileukemic effects in the context of DAC treatment in human myeloid leukemia cell lines. Methods: In our study, we assessed the anti-leukemic effect of EP in the context of DAC treatment by measuring cell proliferation, apoptosis, cell-cycle distribution, and intracellular reactive oxygen species (ROS) levels. Results: Our results showed that the combination of EP and DAC had a more obvious antiproliferative effect than that of DAC as a single agent. EP mainly induced S or G0/G1 phase cell cycle arrest, and DAC arrested the cell cycle in the S or G2/M phase. The combination of EP and DAC had a synergistic effect on cell cycle arrest. Furthermore, single-agent treatment with EP or DAC induced a change in intracellular ROS levels, and the combination of EP and DAC had a synergistic effect on ROS levels, exacerbating leukemia cell death. Conclusion: Our study provides in vitro evidence of the synergistic antileukemic effect and potential mechanisms of the combination of DAC and EP on myeloid leukemia cells.

Aim: Cervical cancer is still one of the most common gynecologic cancers in the world. Since cervical cancer is a potentially preventive cancer, earlier detection is the most effective technique fo...