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Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

ABSTRACT: Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion. Graphical abstract Immunosenescence decreased the antitumor therapeutic efficacy in 16-month-old mice. Sialic acid-mediated photochemotherapy enhanced infiltration of CD8+ T cells and neutrophils into tumors and eliminated the immunosenescence-mediated decline in antitumor therapeutic efficacy.Image 1

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PROVIDER: S-EPMC9939359 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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