Cervical cancer is one of the women-associated tumors that affects numerous people yearly. It is the fourth most common malignancy in women worldwide. Following early diagnosis, this cancer can be cured mainly by traditional methods such as surgery, tumor resection, and chemotherapy; nonetheless, it becomes more challenging to treat in advanced and metastatic stages. With the advent of novel treatments such as angiogenesis inhibitors or immuno-checkpoint blockers in recent years, the survival rate of patients with advanced cervical cancer has significantly increased. However, it has not yet reached a satisfactory level. It has been revealed that human papillomavirus (HPV) infection is responsible for more than 90% of cervical cancer cases. However, evidence revealed that monotherapy with anti-HPV vaccines such as ISA101 could not affect tumor growth and progression in patients with HPV-induced cervical cancer. Therefore, combining ISA101 and immune checkpoint blockers or other immunotherapeutic approaches may be more robust and effective than monotherapy with ISA101 or immune checkpoint blockers for treating cervical cancer. This review summarizes the ISA101 properties, advantages and disadvantages. Furthermore, various conducted combination therapies with ISA101 and the effectiveness and challenges of this treatment have been discussed.

BackgroundThe neutrophil to lymphocyte ratio (NLR) is a cost-effective and easily identifiable inflammatory biomarker that has been shown to be closely associated with tumor prognosis and predict survival in patients with multiple malignancies. However, the predictive value of NLR in patients with gastric cancer (GC) treated with immune checkpoint inhibitors (ICIs) has not been fully explored. Therefore, we conducted a meta-analysis to explore the potential of NLR as a predictor of survival in this population.MethodsWe systematically searched the PubMed, Cochrane Library, and EMBASE databases from inception to the present for observational researches on NLR and its relationship with progression or survival in GC patients receiving ICIs. To assess the prognostic significance of NLR on overall survival (OS) or progression-free survival (PFS), we used fixed or random-effect models to derive and combine hazard ratios (HRs) with 95% confidence intervals (CIs). We also examined the relationship between NLR and treatment efficacy by calculating relative risks (RRs) with 95% CIs for objective response rate (ORR) and disease control rate (DCR) in patients with GC receiving ICIs.ResultsNine studies of 806 patients were eligible. OS and PFS data were obtained from 9 and 5 studies, respectively. In nine studies, NLR was associated with poor survival, the pooled HR was 1.98 (95% CI 1.67- 2.35, p < 0.001), indicating a significant association between high NLR and worse OS. We conducted subgroup analyses based on study characteristics to confirm the robustness of our findings. A relationship between NLR and PFS were reported in five studies with a HR of 1.49 (95% CI 0.99- 2.23, p = 0.056), which was not significantly associated. Pooling four studies that examined the correlation between NLR and ORR/DCR in GC patients, we observed a significant correlation between NLR and ORR (RR = 0.51, p = 0.003), but no significant correlation between NLR and DCR (RR = 0.48, p = 0.111).ConclusionIn summary, this meta-analysis indicates that increased NLR is significantly linked to worse OS in patients with GC receiving ICIs. In addition, lowering NLR can improve ORR. Thus, NLR can serve as a predictor for prognosis and treatment response in GC patients treated with ICIs. Nevertheless, further high-quality prospective studies are required to verify our findings in the future.

BackgroundNecroptosis plays a crucial function in the progression of breast invasive carcinoma (BRCA). It may be triggered in cancer therapy to enhance anti-tumor immunity. However, the functions of necroptosis in tumors and its relationship with the tumor microenvironment (TME) remain largely unclear.MethodsNecroptosis-related genes (NRGs) were collated from high-quality literature reviews. A robust risk model was constructed to systematically evaluate the clinical value, functional status, effects exerted by the risk model on the TME, and the genomic variations based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) meta-cohorts.ResultsA risk model was constructed which comprised of six NRGs, including TNF receptor-associated factor 5 (TRAF5), Toll-like receptor 3 (TLR3), a riboflavin kinase (RFK), Fas ligand (FASLG), Fas-associated protein with death domain (FADD), and baculoviral IAP repeat-containing 3 (BIRC3). The stability and accuracy of the risk model were demonstrated for both the training and validation cohorts and its utility as an independent prognostic model for BRCA was verified. Patients in the low-risk group exhibited “hot” tumors having active immune and cell killing functions, while those in the high-risk group showed “cold” tumors having active tumor proliferation and immunosuppression. Moreover, patients in the high-risk group had a greater number of CNV events in their genome, while the somatic mutations were fewer. Furthermore, patients in the low-risk group showed high sensitivity toward immunotherapy and chemotherapy.ConclusionA reliable risk model based on NRGs to assess patient prognoses and guide clinical decision-making was constructed and validated. Our findings may contribute to the understanding of necroptosis and aid clinical management, along with precision treatment in BRCA.

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