Immunostimulatory biomaterials to boost tumor immunogenicity

Shofolawe-Bakare, Oluwaseyi T.; Stokes, LeAnn S.; Hossain, Mehjabeen; Smith, Adam E.; Werfel, Thomas A.

doi:10.1039/d0bm01183e

Cited by 14 publications

(11 citation statements)

References 189 publications

(293 reference statements)

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“…Our findings indicated that tumor-mediated tolerance or barriers could be overcome by radiation-induced systemic antitumor responses in highly immunogenic tumors and primed CD8 T cells could recognise and attack both local tumors and distant tumors outside the radiation field. In contrast, low immunogenicity indicated that TAAs were downregulated in tumors and evasion of host immunity occurred in the tumor microenvironment, which lacked chemokine-mediated trafficking and showed poor adaptive immune cell activation ( 8 , 11 ). The rarity of the abscopal effect suggests that even primed antitumor CD8 T cells could not overcome a suppressive tumor microenvironment with low infiltration of responding immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer cells that can elicit a protective immune response to inhibit tumor growth are considered to have high immunogenicity. Conversely, cancer cells that only stimulate a weak immune response and fail to control tumor growth are classified as having poor immunogenicity ( 8 ). In this study, we observed the efficacy of radiotherapy in both highly and poorly immunogenic tumor models and found that single high-dose radiation was optimal for stimulating a localised antitumor immune response and provided an opportunity to boost abscopal response rates in highly immunogenic tumors.…”

Section: Introductionmentioning

confidence: 99%

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Abscopal Effects of Local Radiotherapy Are Dependent on Tumor Immunogenicity

et al. 2021

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Although abscopal tumor regression remains a rare phenomenon, interest in exploiting how radiation stimulates the immune system to induce systemic abscopal response is increasing. Here, we tested the hypothesis that tumor immunogenicity determined the ability of radiotherapy to induce abscopal effects. We established highly (MC-38 and E.G7-OVA) or poorly (LL/2 and B16-F10) immunogenic tumor models in this study and treated them with sham radiation, a single dose of 15 Gy, or three fractions of 5 Gy on three consecutive days. Alterations in the tumor microenvironment after radiation were examined by flow cytometry and RNA sequencing. Our results demonstrated the positive correlation between tumor immunogenicity and the abscopal effect of radiotherapy. The single dose of 15 Gy radiation was an effective regimen for inducing abscopal effects in highly immunogenic tumors. Local radiation reshaped the tumor microenvironment of irradiated and non-irradiated distant tumors by increasing CD8 T-cell infiltration and reducing suppressive immune cell accumulation. However, radiation alone was insufficient to elicit abscopal effects in poorly immunogenic tumors. No significant alterations were detected in the non-irradiated distant tumor microenvironment after radiation of poorly immunogenic tumors. In addition, tumor immunogenic subtypes were associated with the radiological response and clinical outcome of patients receiving radiotherapy. These findings indicated that tumor immunogenicity was the dominant characteristic that could predict the abscopal effect of radiotherapy. Our study provides an in-depth understanding of the immunological mechanisms involved in abscopal effects and highlights the impact of tumor heterogeneity on the therapeutic efficacy of radiotherapy and their combination with immunotherapy in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abscopal Effects of Local Radiotherapy Are Dependent on Tumor Immunogenicity

et al. 2021

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“…Injectable or implantable hydrogels and scaffolds, representative of 3D macroscale biomaterials, facilitate the controlled delivery and release of therapeutic small molecule reagents, macromolecule biological factors, and even living cells strikingly heightening the vitality of cancer immunotherapy [ 29 ]. Unfortunately, clinical translations of 3D macroscale biomaterial-based immunotherapies still develop in a slow graded pace during several decades [ 30 , 31 ]. More and more widely recognized, it is essential for the biomaterial engineering researchers to attain a systematic characterization and comprehensive understanding of the mutual interaction between biomaterials and immune system, including how the physicochemical and mechanical properties of the particular biomaterial system influence the immunologic behaviours, and how immunologic indexes fluctuate towards different biomaterial systems upon timescales, in order to speed up their clinical developments [ 7 , 32 , 33 ] ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

Han

2022

Bioactive Materials

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“…Thus, novel immunotherapeutic agents are warranted to overcome this limitation by changing the TME through the depletion of cancer-promoting microenvironmental cells and their reeducation toward immune-stimulating, tumor-suppressive phenotypes [ 13 ]. This strategy is now widely appreciated as an anticancer armamentarium [ 13 , 14 ]. Oncolytic virus (OV) is one of the most promising treatment strategies for solid malignancies [ 15 ] because it can remodel the TME toward a T cell-inflamed phenotype by stimulating host immune responses against the tumor [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Systemic Injection of Oncolytic Vaccinia Virus Suppresses Primary Tumor Growth and Lung Metastasis in Metastatic Renal Cell Carcinoma by Remodeling Tumor Microenvironment

et al. 2022

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Immune checkpoint inhibitors and tyrosine kinase inhibitors are the first-line treatment for metastatic renal cell carcinoma (mRCC), but their benefits are limited to specific patient subsets. Here, we aimed to evaluate the therapeutic efficacy of JX-594 (pexastimogene devacirepvec, Pexa-vec) monotherapy by systemic injection in comparison with sunitinib monotherapy in metastatic orthotopic RCC murine models. Two highly metastatic orthotopic RCC models were developed to compare the treatment efficacy in the International Metastatic RCC Database Consortium favorable-risk and intermediate- or poor-risk groups. JX-594 was systemically injected through the peritoneum, whereas sunitinib was orally administered. Post-treatment, tumor microenvironment (TME) remodeling was determined using immunofluorescence analysis. Systemic JX-594 monotherapy injection demonstrated therapeutic benefit in both early- and advanced-stage mRCC models. Sunitinib monotherapy significantly reduced the primary tumor burden and number of lung metastases in the early-stage, but not in the advanced-stage mRCC model. Systemic JX-594 delivery remodeled the primary TME and lung metastatic sites by increasing tumor-infiltrating CD4/8+ T cells and dendritic cells. Systemic JX-594 monotherapy demonstrated significantly better therapeutic outcomes compared with sunitinib monotherapy in both early- and advanced-stage mRCCs by converting cold tumors into hot tumors. Sunitinib monotherapy effectively suppressed primary tumor growth and lung metastasis in early-stage mRCC.

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Immunostimulatory biomaterials to boost tumor immunogenicity

Abstract: Cancer immunotherapy is exhibiting great promise as a new therapeutic modality for cancer treatment. However, immunotherapies are limited by the inability of some tumors to provoke an immune response. These...

Cited by 14 publications

References 189 publications

Abscopal Effects of Local Radiotherapy Are Dependent on Tumor Immunogenicity

Abscopal Effects of Local Radiotherapy Are Dependent on Tumor Immunogenicity

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

Systemic Injection of Oncolytic Vaccinia Virus Suppresses Primary Tumor Growth and Lung Metastasis in Metastatic Renal Cell Carcinoma by Remodeling Tumor Microenvironment

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