In situ immunization aims at generating antitumor immune responses through manipulating the tumor microenvironment. Based on recent advances in the understanding of antitumor immunity, we designed a three-step approach to in situ immunization to lymphoma: (1) Inducing immunogenic tumor cell death with the chemotherapeutic drug Doxorubicin (Dox). Dox enhances the expression of "eat-me" signals by dying tumor cells, facilitating their phagocytosis by dendritic cells (DCs). Due to the vesicant activity of Dox, microparticles (MPs) made of PLGA (a biodegradable polymer) can safely deliver Dox intratumorally and are effective vaccine adjuvants; (2) Enhancing T cell activation using anti-OX40; (3) Sustaining T cell responses by checkpoint blockade using anti-CTLA-4. In vitro, Dox MPs were less cytotoxic to DCs than to B lymphoma cells, did not require internalization by tumor cells, and significantly enhanced phagocytosis of tumor cells by DCs as compared to soluble Dox. In mice, this three-step therapy induced CD4- and CD8-dependent systemic immune responses that enhanced T cell infiltration into distant tumors leading to their eradication and significantly improving survival. Our findings demonstrate that systemic antitumor immune responses can be generated locally by three-step therapy and merit further investigation as an immunotherapy for lymphoma patients.
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 June 2019.
All research outputs
#6,960,303
of 32,502,987 outputs
Outputs from Cancer Immunology Research
#780
of 1,844 outputs
Outputs of similar age
#70,795
of 298,363 outputs
Outputs of similar age from Cancer Immunology Research
#24
of 37 outputs
Altmetric has tracked 32,502,987 research outputs across all sources so far. Compared to these this one has done well and is in the 78th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,844 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.4. This one has gotten more attention than average, scoring higher than 57% of its peers.
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