Neoantigens in precision cancer immunotherapy:from identification to clinical applications

Immunotherapies targeting cancer neoantigens are safe,effective,and precise.Neoantigens can be identified mainly by genomic techniques such as next-generation sequencing and high-throughput single-cell sequencing;proteomic techniques such as mass spectrometry;and bioinformatics tools based on high-throughput sequencing data,mass spectrometry data,and biological databases.Neoantigen-related therapies are widely used in clinical practice and include neoantigen vaccines,neoantigen-specific CD8+and CD4+T cells,and neoantigen-pulsed dendritic cells.In addition,neoantigens can be used as biomarkers to assess immunotherapy response,resistance,and prognosis.Therapies based on neoantigens are an important and promising branch of cancer immunotherapy.Unremitting efforts are needed to unravel the comprehensive role of neoantigens in anti-tumor immunity and to extend their clinical application.This review aimed to summarize the progress in neoantigen research and to discuss its opportunities and challenges in precision cancer immunotherapy.

Current Status and Future Perspective of Immunotherapy in Gastrointestinal Cancers

Gastrointestinal(GI)cancers represent a major public health problem worldwide.Due to the late detection and high heterogeneity of GI cancers,traditional treatments,including surgery,radiotherapy,chemotherapy,and targeted therapy,have shown limited effects,and the overall prognosis of these patients remains poor.Recently,immunotherapy,involving programmed cell death-1(PD-1)and its ligand(PD-L1),has shown promising efficacy in several solid cancers and seems to have become a potential treatment option for GI cancers This review focuses on data on the development of immunotherapy-based clinical trials in esophageal cancer,gastric cancer,and colorectal cancer.The predictive biomarkers and combination strategies in clinical trials and translational medicine are also discussed.Finally,prospects for immunotherapy in the treatment of GI cancers are described.Although only a small proportion of patients with GI cancers respond to PD-1/PD-L1 blockade,we strongly believe that precision immunotherapy might improve the overall survival of many more GI cancer patients in the future.

Dual-targeting prodrug nanotheranostics for NIR-Ⅱfluorescence imaging-guided photo-immunotherapy of glioblastoma

Glioblastoma(GBM) therapy is severely impaired by the blood-brain barrier(BBB) and invasive tumor growth in the central nervous system.To improve GBM therapy,we herein presented a dual-targeting nanotheranostic for second near-infrared(NIR-Ⅱ) fluorescence imaging-guided photoimmunotherapy.Firstly,a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor(D-A-D) backbone was synthesized.Then,the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1(JPC) and T7 ligand-modified PEG5k-DSPE.T7 can cross the BBB for tumor-targeted delivery of JPC and MRP.JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells.MRP could generate NIR-Ⅱ fluorescence to navigate 808 nm laser,induce a photothermal effect to trigger in-situ antigen release at the tumor site,and ultimately elicit antitumor immunogenicity.Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo.The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.