The abscopal effect: inducing immunogenicity in the treatment of brain metastases secondary to lung cancer and melanoma

Tracz, Jovanna A.; Donnelly, Brianna M.; Ngu, Sam; Vojnic, Morana; Wernicke, A. Gabriella; D’Amico, Randy S.

doi:10.1007/s11060-023-04312-8

Cited by 7 publications

(2 citation statements)

References 56 publications

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“…The recent literature indicates that concurrent ICI and SRS association may increase OS and enhance abscopal responses in brain metastasis patients [30], with no convincing significant differences in radionecrosis, intralesional hemorrhage, or other TRICs incidence versus SRS alone. As most of the published studies on ICI-SRS association focus on melanoma and NSCLC brain metastasis patients, those conclusions should be taken cautiously when applied to other cancer types (i.e.…”

Section: Discussionmentioning

confidence: 99%

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

Botticella,

Dhermain

2023

Current Opinion in Neurology

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Purpose of review The incidence of brain metastasis is high and still increasing. Among local therapies, stereotactic radiosurgery (SRS) is an effective treatment option, optimally sparing normal brain, even for multiple brain metastases. Immune checkpoint inhibitors (ICIs) become the new standard of care in an increasing number of cancers, and the combination SRS and ICI is often proposed to patients, but few data have been published on the efficacy and the toxicity of this association. Recent findings Explaining this lack of consensus: retrospective studies with different primary cancers, various treatment lines and unknown levels of steroid exposure. Concerning the toxicity, the independent association of radionecrosis with brain-PTV volume was confirmed, and a decreased dose of SRS is now tested in a randomized study. Finally, a ‘concurrent’ delivery of SRS and ICI (within a 4 weeks’ interval) seems the optimal schedule; fractionated radiosurgery for large brain metastasis should be favored. Radio-sensitizing nanoparticles and devices aiming to increase the permeability of the blood brain barrier should be considered in future combinations. Summary The efficacy/toxicity balance of SRS-ICI combination should be regularly re-evaluated, anticipating continued progress in ICI and SRS delivery, with more long-survivors potentially exposed to long-term toxicities. Patients should be included in clinical trials and clearly informed to participate more closely in the final choice.

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Section: Discussionmentioning

confidence: 99%

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

Botticella,

Dhermain

2023

Current Opinion in Neurology

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“…The combination of RT and immunotherapy with ICI (antibody therapies against CTLA-4, PD-1) has an abscopal effect, respectively; localized radiation has the ability to induce an antitumor response at distant sites that were not subjected to targeted RT [7,9,10].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy Combined with Radiation in Malignant Melanoma without BRAF Mutations Brain Metastases—Favorable Response after Immunotherapy Continued beyond Progression

Rahnea-Nita,

Rebegea,

Toma

et al. 2024

JPM

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We present the case of a patient who was diagnosed in 2018 with nodular Malignant Melanoma (MM) without BRAF V 600 mutations stage 3 C (pT4b pN1a M0), and who underwent adjuvant citokines treatment with Interferon alpha 2b-48 weeks. Immunotherapy was initiated in January 2021 for lung and lymph node metastases. In June 2021, there was a partial response of the lung and lymph node metastases, but there was also progression to brain metastases. Immunotherapy was continued and Whole Brain Radiotherapy (WBRT) was performed. In September 2023, the imaging investigations revealed a favorable response, with no lesions suggestive of secondary determinations. The combination of Radiotherapy (RT) and Immunotherapy (IT) with Immune Checkpoint Inhibitors (ICI) has an abscopal effect. There is a coordinated action in the combination of RT and IT in order to obtain a common result, with the antitumor effect being greater than if RT or IT acted separately.

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Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells

Wang,

Yan,

Guo

et al. 2024

Adv Healthcare Materials

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Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor‐associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the “three‐in‐one” IAHA‐LaP/siPTPN6 NPs containing lanthanum ions (La3+), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La3+ significantly promotes cGAMP‐mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF‐κB p65. Moreover, the IAHA‐LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF‐κB p65 and augment K63‐linked ubiquitination of STING protein via siPTPN6‐mediated downregulation of SHP‐1 protein. Furthermore, NPs improve the secretion of IFNβ (2.4‐fold), IL‐6 (1.5‐fold), and TNF‐α (1.4‐fold), thereby promoting DCs maturation compared to the mixture of La3+ and cGAMP. In vivo results show that the IAHA‐LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor‐draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8+T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti‐tumor immunity and generating a long‐term anti‐tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA‐LaP/siPTPN6 NPs may offer a promising platform for robust anti‐tumor immune responses.

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The abscopal effect: inducing immunogenicity in the treatment of brain metastases secondary to lung cancer and melanoma

Cited by 7 publications

References 56 publications

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

Immunotherapy Combined with Radiation in Malignant Melanoma without BRAF Mutations Brain Metastases—Favorable Response after Immunotherapy Continued beyond Progression

Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells

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