FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308394842> ?p ?o ?g. }

• W4308394842 abstract "<h3>Background</h3> Agents that modulate the tumor microenvironment (TME) to promote anti-tumor effects are desirable for the therapy of solid tumors. Recombinant Listeria-monocytogenes vaccine consisting of the fusion protein of truncated Listeriolysin O and tumor-associated antigen (TAA) is an established strategy to improve antigen-specific T cell response for cancer immunotherapy. CD105 is a co-receptor for the TGF-beta signaling cascade. Due to its elevated expression in many cancer types, including renal cell carcinoma (RCC), CD105 is characterized as a TAA of therapeutic potential. Here we evaluated the efficacy and immunomodulatory effects of a Listeria-based vaccine encoding CD105 (Lm-LLO-CD105A) for the therapy of renal cell carcinoma (RCC) in a murine model. <h3>Methods</h3> Murine RCC cell line (Renca) cells were implanted subcutaneously or orthotopically into male Balb/c mice. Subsequently, mice were vaccinated with PBS, Lm-LLO-CD105A, or Control Lm weekly for three weeks, and tumor progression was routinely monitored. Splenocytes and subcutaneous and orthotopic tumor tissues were immunophenotyped by flow cytometry. Lymphocyte depletion experiments were carried out in subcutaneous and orthotopic models to evaluate the immune subset responsible for the anti-tumoral effect of the recombinant Listeria-based vaccine. <h3>Results</h3> In both models, vaccination with Lm-LLO-CD105A led to significant control of tumor growth compared to placebo and Control Lm (figure 1). This antigen-specific vaccine promoted tumor control by significantly improving the infiltration of effector CD8⁺ T and CD4⁺T cells into the TME. The CD8⁺ T cells are polyfunctional and characterized by profound production of inflammatory cytokines, including IFN-g, IL-2, and TNF-a, but the functionality of the CD4⁺ T cells was not as robust. Similarly, the systemic cytotoxic response demarcated by IFN-g⁺IL-2 ⁺ TNF -a ⁺ producing splenic CD8⁺ T cells was highly potent upon Lm-LLO-CD105A vaccination. Further, in both subcutaneous and orthotopic models, the TME was polarized from an immunosuppressive phenotype to an inflamed phenotype characterized by a reduction in the CD4⁺ Foxp3⁺Treg population and a reduced population of MDSCs (CD11b⁺Gr1⁺) in the kidney TME. Not surprisingly, the antitumor effect was completely abrogated when Lm-LLO-CD105A was utilized in the presence of a CD8⁺ T cell-depleting antibody (figure 2) <h3>Conclusions</h3> Lm-LLO-CD105A effectively controlled subcutaneous and orthotopic kidney tumors. This efficacy depended on the profound infiltration of cytokine-producing CD8⁺ T cells and the reduction of suppressive immune subsets in the TME. Altogether our data suggest that tumor targeting with a Listeria-based approach is an effective strategy to modulate the TME for effective control of renal cell carcinoma. <h3>Ethics Approval</h3> All studies involving animals were carried out in accordance with ethical standards of the Texas Tech University Health Sciences Center under the IACUC protocol number 17018" @default.
• W4308394842 created "2022-11-11" @default.
• W4308394842 creator A5011838979 @default.
• W4308394842 creator A5086312125 @default.
• W4308394842 date "2022-11-01" @default.
• W4308394842 modified "2023-09-27" @default.
• W4308394842 title "1180 Listeria-based immunotherapy sculpts CD8⁺T cell response in the tumor microenvironment to control renal cell carcinoma" @default.
• W4308394842 doi "https://doi.org/10.1136/jitc-2022-sitc2022.1180" @default.
• W4308394842 hasPublicationYear "2022" @default.
• W4308394842 type Work @default.
• W4308394842 citedByCount "1" @default.
• W4308394842 countsByYear W43083948422023 @default.
• W4308394842 crossrefType "proceedings-article" @default.
• W4308394842 hasAuthorship W4308394842A5011838979 @default.
• W4308394842 hasAuthorship W4308394842A5086312125 @default.
• W4308394842 hasBestOaLocation W43083948421 @default.
• W4308394842 hasConcept C147483822 @default.
• W4308394842 hasConcept C154317977 @default.
• W4308394842 hasConcept C167672396 @default.
• W4308394842 hasConcept C202751555 @default.
• W4308394842 hasConcept C203014093 @default.
• W4308394842 hasConcept C2776107976 @default.
• W4308394842 hasConcept C2776662205 @default.
• W4308394842 hasConcept C2777701055 @default.
• W4308394842 hasConcept C2780674031 @default.
• W4308394842 hasConcept C502942594 @default.
• W4308394842 hasConcept C55493867 @default.
• W4308394842 hasConcept C71924100 @default.
• W4308394842 hasConcept C86803240 @default.
• W4308394842 hasConcept C8891405 @default.
• W4308394842 hasConceptScore W4308394842C147483822 @default.
• W4308394842 hasConceptScore W4308394842C154317977 @default.
• W4308394842 hasConceptScore W4308394842C167672396 @default.
• W4308394842 hasConceptScore W4308394842C202751555 @default.
• W4308394842 hasConceptScore W4308394842C203014093 @default.
• W4308394842 hasConceptScore W4308394842C2776107976 @default.
• W4308394842 hasConceptScore W4308394842C2776662205 @default.
• W4308394842 hasConceptScore W4308394842C2777701055 @default.
• W4308394842 hasConceptScore W4308394842C2780674031 @default.
• W4308394842 hasConceptScore W4308394842C502942594 @default.
• W4308394842 hasConceptScore W4308394842C55493867 @default.
• W4308394842 hasConceptScore W4308394842C71924100 @default.
• W4308394842 hasConceptScore W4308394842C86803240 @default.
• W4308394842 hasConceptScore W4308394842C8891405 @default.
• W4308394842 hasLocation W43083948421 @default.
• W4308394842 hasOpenAccess W4308394842 @default.
• W4308394842 hasPrimaryLocation W43083948421 @default.
• W4308394842 hasRelatedWork W2548277325 @default.
• W4308394842 hasRelatedWork W2804415345 @default.
• W4308394842 hasRelatedWork W2898701288 @default.
• W4308394842 hasRelatedWork W2904909612 @default.
• W4308394842 hasRelatedWork W3025154575 @default.
• W4308394842 hasRelatedWork W4281389645 @default.
• W4308394842 hasRelatedWork W4286629873 @default.
• W4308394842 hasRelatedWork W4291378227 @default.
• W4308394842 hasRelatedWork W4304979265 @default.
• W4308394842 hasRelatedWork W4378715746 @default.
• W4308394842 isParatext "false" @default.
• W4308394842 isRetracted "false" @default.
• W4308394842 workType "article" @default.