Exosomes in cancer immunoediting and immunotherapy

As an important means of communication among cells,exosomes are being studied more and more widely,especially in the context of cancer immunotherapy.In the phase of tumor immunoediting,exosomes derived from tumor cells and different immune cells have complex and changeable physiological functions,because they carry different proteins and nucleic acid from the source cells.Based on the role of exosomes in the communication between different cells,cancer treatment methods are also under continuous research.This review briefly introduces the molecular composition of exosomes,which is closely related to their secretion mechanism.Subsequently,the role of exosomes encapsulating different information molecules is summarized.The role of exosomes in the three phases of tumor immunoediting is introduced in detail,and the relevant literature of exosomes in the tumor immunemicroenvironment is summarized by using a novel framework for extracting relevant documents.Finally,it summarizes the various exosome-based immunotherapies currently proposed,as well as the challenges and future prospects of exosomes in tumor immunotherapy.

Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold

In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity.To break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune responses.Upon response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity rises.Subsequently,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T cells.Finally,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor effects.Therefore,cancer immunoediting phases reverse and systemic antitumor immune responses occur.TURN achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in vivo.Taken together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.

Pi(Spleen)-Deficiency Syndrome in Tumor Microenvironment Is the Pivotal Pathogenesis of Colorectal Cancer Immune Escape

Cancer immunoediting consists of three sequential phases： elimination, equilibdum, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibdum phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi （Spteen）-deficiency. Ctassic quotations, immune evidence and ctinicat observations suggest that Spleen （but not other organs） deficiency is the key pathogenesis of colorectal cancer （CRC） microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-dedved immunosuppressive factors and surrendered immune cells--regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages （TAMs） constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.