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Recent Advancements in Nanomedicine for 'Cold' Tumor Immunotherapy.

ABSTRACT: Although current anticancer immunotherapies using immune checkpoint inhibitors (ICIs) have been reported with a high clinical success rate, numerous patients still bear 'cold' tumors with insufficient T cell infiltration and low immunogenicity, responding poorly to ICI therapy. Considering the advancements in precision medicine, in-depth mechanism studies on the tumor immune microenvironment (TIME) among cold tumors are required to improve the treatment for these patients. Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy, activates immune function, modulates the TIME, and has been applied in combination with other anticancer therapeutic strategies. This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies, as well as a brief talk about the feasibility of clinical translation.

SUBMITTER: Chen Q

PROVIDER: S-EPMC8006526 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Recent Advancements in Nanomedicine for 'Cold' Tumor Immunotherapy.

Chen Qinjun Q Sun Tao T Jiang Chen C

Nano-micro letters 20210316 1

Although current anticancer immunotherapies using immune checkpoint inhibitors (ICIs) have been reported with a high clinical success rate, numerous patients still bear 'cold' tumors with insufficient T cell infiltration and low immunogenicity, responding poorly to ICI therapy. Considering the advancements in precision medicine, in-depth mechanism studies on the tumor immune microenvironment (TIME) among cold tumors are required to improve the treatment for these patients. Nanomedicine has emerg ...[more]

PMID: 34138315

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Project description:Colorectal cancer (CRC), mostly categorized as a low immunogenic microsatellite-stable phenotype bearing complex immunosuppressive tumor microenvironment (TME), is highly resistant to immunotherapy. Seeking safe and efficient alternatives aimed at modulating tumor immunosuppressive TME to improve outcome of CRC is highly anticipated yet remains challenging. Methods: Enlightened from the drug complementary art in traditional Chinese medicine, we designed a self-assembled nanomedicine (termed LNT-UA) by the natural active ingredients of ursolic acid (UA) and lentinan (LNT) through a simple nano-precipitation method, without any extra carriers, for CRC immunotherapy. Results: UA induces immunogenic cell death (ICD), while LNT further promotes dendritic cell (DC) maturation and repolarizes tumor-associated macrophage (TAM) from a protumorigenic M2 to an antitumor M1 phenotype. Co-delivery of UA and LNT by LNT-UA effectively reshapes the immunosuppressive TME and mobilizes innate and adaptive immunity to inhibit tumor progression in the CT26 CRC tumor model. Following the principle of integrative theoretical system of traditional Chinese medicine (TCM) on overall regulation, the further combination of LNT-UA and anti-CD47 antibody (αCD47) would reinforce the antitumor immunity by promoting phagocytosis of dying tumor cells and tumor-associated antigens (TAAs), leading to effective suppression of both primary and distant tumor growth with 2.2-fold longer of median survival time in the bilateral tumor model. Most notably, this combination effect is also observed in the spontaneous CRC model induced by chemical carcinogens, with much less and smaller size of tumor nodules after sequential administration of LNT-UA and αCD47 through gavage and intraperitoneal injection, respectively. Conclusions: This study provides a promising self-assembled traditional Chinese nanomedicine to improve immunotherapy for CRC, which might be applicable for future clinical translation.

Dataset Information

Recent Advancements in Nanomedicine for 'Cold' Tumor Immunotherapy.

Publications

Recent Advancements in Nanomedicine for 'Cold' Tumor Immunotherapy.

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