RESUMEN
Conventional treatments have shown a limited efficacy for pancreatic cancer, and immunotherapy is an emerging option for treatment of this highly fatal malignancy. Neoantigen is critical to improving the efficacy of tumor-specific immunotherapy. The cancer and peripheral blood specimens from human leukocyte antigen (HLA)-A0201 positive pancreatic cancer patient were subjected to next-generation sequencing and bioinformatics analyses were performed to screen high-affinity and highly stable neoepitopes. The activation of cytotoxic T lymphocytes (CTLs) by the mutBCL2A111-20 neoepitope targeting B-cell lymphoma 2-related protein A1 (BCL2A1) mutant epitope was investigated, and the cytotoxicity of mutBCL2A111-20 neoepitope-specific CTLs to pancreatic cancer cells was evaluated. The mutBCL2A111-20 neoepitope was found to present a high immunogenicity and induce CTLs activation and proliferation, and was cytotoxic to mutBCL2A111-20 neoepitope-loaded T2 cells and pancreatic cancer PANC-1-Neo and A2-BxPC-3-Neo cells that overexpressed mutBCL2A111-20 neoepitopes, appearing a targeting neoepitope specificity. In addition, high BCL2A1 expression correlated with a low 5-year progress free interval (PFI) among pancreatic cancer patients. Our findings provide experimental supports to individualized T-cell therapy targeting mutBCL2A111-20 neoepitopes, and provide an option of immunotherapy for pancreatic cancer.
RESUMEN
As an asphalt modifier, waste polypropylene (RPP) can not only optimize the performance of asphalt but also greatly alleviate the problem of waste plastic treatment, effectively reducing environmental pollution and resource waste. In order to evaluate the influence of RPP and styrene butadiene styrene (SBS) on asphalt performance, the application of RPP in modified asphalt pavement has been expanded. In this study, a dynamic shear rheometer (DSR), bending beam rheometer (BBR) and other instruments were used to evaluate the rheological properties of composite-modified asphalt. Fourier infrared spectroscopy (FTIR) and fluorescence microscopy (FM) was employed to conduct a microscopic analysis of the modified asphalt, and the layer analysis method was adopted to determine the optimal RPP content. The test results show that the rheological properties of asphalt are significantly improved by the composite modification of RPP and SBS. In addition, the cross-linking between polymer and asphalt is further enhanced by the composite addition of RPP and SBS. The comprehensive performance of modified asphalt is optimized at the RPP content of 2%, which is suitable for applications in the cold temperate zone. The RPP/SBS composite-modified asphalt is able to improve the utilization rate of RPP and has good environmental and economic benefits, thus exhibiting excellent comprehensive performance. However, the optimal asphalt content in the mixture was not investigated, and the economic benefits brought by the utilization of RPP were not evaluated and require further study.
RESUMEN
The efficacy of conventional treatments for pancreatic cancer remains unsatisfactory, and immunotherapy is an emerging option for adjuvant treatment of this highly deadly disorder. The tumor-associated antigen (TAA) MUC1 is expressed in a variety of human cancers and is overexpressed in more than 90% of pancreatic cancer, which makes it an attractive target for cancer immunotherapy. As a self-protein, MUC1 shows a low immunogenicity because of immune tolerance, and the most effective approach to breaking immune tolerance is alteration of the antigen structure. In this study, the altered MUC11068-1076Y1 epitope (YLQRDISEM) by modification of amino acid residues in sequences presented a higher immunogenicity and elicited more CTLs relative to the wild-type (WT) MUC11068-1076 epitope (ELQRDISEM). In addition, the altered MUC11068-1076Y1 epitope was found to cross-recognize pancreatic cancer cells expressing WT MUC1 peptides in an HLA-A0201-restricted manner and trigger stronger immune responses against pancreatic cancer via the perforin/granzyme apoptosis pathway. As a potential HLA-A0201-restricted CTL epitope, the altered MUC11068-1076Y1 epitope is considered as a promising target for immunotherapy of pancreatic cancer. Alteration of epitope residues may be feasible to solve the problem of the low immunogenicity of TAA and break immune tolerance to induce immune responses against human cancers.