Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membranes modified by mannose. Poly(d,l-lactide- co-glycolide) nanoparticles are first loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification with mannose moiety (NP-R@M-M), the obtained nanovaccine shows enhanced uptake by antigen presenting cells such as dendritic cells, which would then be stimulated to the maturation status to trigger antitumor immune responses. With great efficacy to delay tumor development as a prevention vaccine, vaccination with such NP-R@M-M in combination with checkpoint-blockade therapy further demonstrates outstanding therapeutic efficacy to treat established tumors. Therefore, our work presents an innovative way to fabricate cancer nanovaccines, which in principle may be applied for a wide range of tumor types.

BackgroundThere is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment.MethodsWe searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.ResultsA total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR = 0.578, 95% CI 0.522–0.641, P < 0.001) and PFS (HR = 0.598, 95% CI 0.465–0.768, P < 0.001). The effect of LMR on OS was observed among various tumor types. A higher pretreatment LMR was associated with improved OS in chemotherapy (n = 10, HR = 0.592, 95% CI 0.518–0.676, P < 0.001), surgery (n = 10, HR = 0.683, 95% CI 0.579–0.807, P < 0.001) and combined therapy (n = 11, HR = 0.507, 95% CI 0.442–0.582, P < 0.001) in the subgroup analysis by different therapeutic strategies. The cut-off value for LMR was 3.0 (range = 2.35–5.46). Subgroup analysis according to the cut-off value showed a significant prognostic value of LMR on OS and PFS in both subgroups.ConclusionsA high pretreatment LMR is associated with favorable clinical outcomes in advanced-stage epithelial cancers undergoing different therapeutic strategies. LMR could be used to improve clinical decision-making regarding treatment in advanced epithelial cancers.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0698-5) contains supplementary material, which is available to authorized users.

Background: We aimed to characterize the relationships of lymphocyte activation gene-3 (LAG-3) expression, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression, and CD8 + tumor-infiltrating lymphocyte (TIL) density, and to investigate the joint prognostic impact of these three markers in patients with surgically resected esophageal squamous cell carcinoma (ESCC).Methods: Expression of LAG-3, CTLA-4 and the density of CD8 + TILs were evaluated by immunohistochemistry in resected ESCC. The associations between LAG-3 expression and clinicopathologic characteristics, as well as patient prognoses, were analyzed.Results: A total of 183 patients were included. LAG-3 expression was observed in 69 (37.7%) patients.Positive LAG-3 expression was significantly associated with CTLA-4 expression (P=0.004). LAG-3 positivity, CTLA-4 positivity, and low CD8 + TIL densities were significantly associated with worsening recurrence-free survival (RFS) [LAG-3: hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.10-2.89; P=0.

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The development of effective cancer vaccines is an important direction in the area of cancer immunotherapy. Although certain types of preventive cancer vaccines have already been used in the clinic, therapeutic cancer vaccines for treatment of already established tumors are still in high demand. In this study, we develop a new type of cancer vaccine by mixing cellpenetrating peptide (CPP) conjugated antigen as the enhanced antigen, together with CpG as the immune adjuvant. A special CPP, cytosol-localizing internalization peptide 6 (CLIP6), which has the ability to enter cells exclusively via a nonendosomal mechanism, i.e., direct translocation across the cell membrane, is conjugated with model antigen ovalbumin (OVA). Compared to naked OVA, the obtained CLIP6-OVA conjugates show greatly increased uptake by dendritic cells (DCs) and, more importantly, remarkably enhanced antigen cross-presentation, eliciting stronger cytotoxic T lymphocyte (CTL) mediated immune responses with the help of CpG. This CLIP6-OVA/CpG formulation offers effective protection for mice against challenged B16-OVA tumors, and is able to further function as a therapeutic vaccine, which, in combination with immune checkpoint blockade therapy, can significantly suppress the alreadyestablished tumors. Such a CLIP6-based cancer vaccine developing strategy shows promising potential toward clinical practice owing to its features of easy preparation, low cost, and remarkable biocompatibility.