Boosting the Abscopal Effect Using Immunogenic Biomaterials With Varying Radiation Therapy Field Sizes.
Journal
International journal of radiation oncology, biology, physics
ISSN: 1879-355X
Titre abrégé: Int J Radiat Oncol Biol Phys
Pays: United States
ID NLM: 7603616
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
23
02
2021
revised:
31
08
2021
accepted:
03
09
2021
pubmed:
17
9
2021
medline:
8
3
2022
entrez:
16
9
2021
Statut:
ppublish
Résumé
Persistent immunosuppression in the tumor microenvironment is a major limitation to boosting the abscopal effect, whereby radiation therapy at 1 site can lead to regression of tumors at distant sites. Here, we investigate the use of radiation and immunogenic biomaterials (IBM) targeting only the gross tumor volume/subvolume for boosting the abscopal effect in immunologically cold tumors. To evaluate the abscopal effect, 2 syngeneic contralateral tumors were implanted in each mouse, where only 1 tumor was treated. IBM was administered to the treated tumor with 1 fraction of radiation and results were compared, including as a function of different radiation therapy field sizes. The IBM was designed similar to fiducial markers using immunogenic polymer components loaded with anti-CD40 agonist. Tumor volumes of both treated and untreated tumors were measured over time, along with survival and corresponding immune cell responses. Results showed that radiation with IBM administered to the gross tumor subvolume can effectively boost abscopal responses in both pancreatic and prostate cancers, significantly increasing survival (P < .0001 and P < .001, respectively). Results also showed equal or superior abscopal responses when using field sizes smaller than the gross tumor volume compared with irradiating the whole tumor volume. These results were buttressed by observation of higher infiltration of cytotoxic CD8+ T-lymphocytes in the treated tumors (P < .0001) and untreated tumors (P < .0001) for prostate cancer. Significantly higher infiltration was also observed in treated tumors (P < .0001) and untreated tumors P < .01) for pancreatic cancer. Moreover, the immune responses were accompanied by a positive shift of proinflammatory cytokines in both prostate and pancreatic tumors. The approach targeting gross tumor subvolumes with radiation and IBM offers opportunity for boosting the abscopal effect while significantly minimizing healthy tissue toxicity. This approach proffers a radioimmunotherapy dose-painting strategy that can be developed for overcoming current barriers of immunosuppression especially for immunologically cold tumors.
Identifiants
pubmed: 34530092
pii: S0360-3016(21)02793-0
doi: 10.1016/j.ijrobp.2021.09.010
pmc: PMC8750216
mid: NIHMS1754769
pii:
doi:
Substances chimiques
Biocompatible Materials
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
475-486Subventions
Organisme : NCI NIH HHS
ID : R01 CA239042
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA205094
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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