Immunotherapy Plus Radiotherapy for the Treatment of Sarcomas: Is There a Potential for Synergism?

Wang, Jiaqiang; Ge, Hong; Tian, Zhichao

doi:10.2147/ott.s410693

Cited by 3 publications

(5 citation statements)

References 114 publications

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“…Tumors frequently develop immunosuppressive mechanisms that can reduce the efficiency of the radscopal effect, and the best radiation dosages and fractionation schedules to produce it are still unknown. The clinical usefulness of RT is further complicated by difficulties in tracking and evaluating its systemic effects ( Wang et al, 2023 ).…”

Section: Radscopal Effectmentioning

confidence: 99%

“…Selecting the optimal dose of RT involves considering factors such as tumor characteristics, treatment intent (curative vs palliative), radiation sensitivity, normal tissue tolerance, treatment schedule, patient factors, and clinical guidelines. Treatment planning tools and sophisticated imaging methods aid in ensuring that the tumor receives a precise dose while neighbouring healthy tissues are spared ( Wang et al, 2023 ). Close monitoring during treatment enables adjustments based on toxicity and tumor response.…”

Section: Optimal Rt Dose-fractionation Schedulementioning

confidence: 99%

“…Radiation may more readily destroy some cells while sparing more resilient ones. Plans for radiation therapy can be adjusted to take these variations into consideration in order to maximize treatment efficacy and reduce harm to healthy tissue ( Wang et al, 2023 ).…”

Section: Optimal Rt Dose-fractionation Schedulementioning

confidence: 99%

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The future of cancer treatment: combining radiotherapy with immunotherapy

Dagar,

Gupta,

Shankar

et al. 2024

Front. Mol. Biosci.

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Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other’s beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell’s genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy.

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Section: Radscopal Effectmentioning

confidence: 99%

Section: Optimal Rt Dose-fractionation Schedulementioning

confidence: 99%

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The future of cancer treatment: combining radiotherapy with immunotherapy

Dagar,

Gupta,

Shankar

et al. 2024

Front. Mol. Biosci.

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“…RT can lyse the immune cells locally. It can increase immune suppressive cells, signal pathways, and immune suppressive factors [76]. Hence, synchronizing the SBRT and IMT sequences is critical.…”

Section: Sbrt-imt Timingmentioning

confidence: 99%

“…In conclusion, several critical conditions for cyclical/intermittent single-dose ISVRT are 1. overcoming the hypoxia immune-suppressive environment is the sine qua non for a successful in situ vaccination approach; 2. generating significant neoantigens/neoepitopes for a dynamic/adoptive in situ vaccination effect; 3. expanding the repertoire and repeated stimulations-booster vaccine effects and eliciting and enhancing innate immune memory cell pathways; 4. using appropriate immune adjuvants (including nanomedicines) to enhance the in situ vaccination effect, as in standard vaccination techniques against infections; 5. countering the "immunosuppressive recoil" of "concomitant immune tolerance" demonstrated by the tumor that are outside the field of radiation [101]; 6. expanding the four-dimensional effect of the number of neoantigens, widening the spectrum of antigens in different mutational types, intensifying antigenicity, and adapting to the trunk, branch, and private mutational evolution over time. Both the quantity and density of activated CD8+ cells [76] matter in the immune-therapy-induced response. Since the algorithm is complex and multifactorial, using the multiarm-multistage (MAMS) clinical trials method may be necessary, where multiple experimental treatments tested against a control arm within the same trial have several advantages in terms of time and resource consumption compared to when conducted as separate trials [102].…”

Section: Summary and Limitations Of The Articlementioning

confidence: 99%

Therapeutic In Situ Cancer Vaccine Using Pulsed Stereotactic Body Radiotherapy—A Translational Model

Swamy

2023

Vaccines

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Both radiation and cancer therapeutic vaccine research are more than 100 years old, and their potential is likely underexplored. Antiangiogenics, nanoparticle targeting, and immune modulators are some other established anticancer therapies. In the meantime, immunotherapy usage is gaining momentum in clinical applications. This article proposes the concept of a pulsed/intermittent/cyclical endothelial-sparing single-dose in situ vaccination (ISVRT) schedule distinguishable from the standard therapeutic stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) plans. This ISVRT schedule can repeatedly generate tumor-specific neoantigens and epitopes for primary and immune modulation effects, augment supplementary immune enhancement techniques, activate long-term memory cells, avoid extracellular matrix fibrosis, and essentially synchronize with the vascular normalized immunity cycle. The core mechanisms of ISVRT impacting in situ vaccination would be optimizing cascading antigenicity and adjuvanticity. The present proposed hypothesis can be validated using the algorithm presented. The indications for the proposed concept are locally progressing/metastatic cancers that have failed standard therapies. Immunotherapy/targeted therapy, chemotherapy, antiangiogenics, and vascular–lymphatic normalization are integral to such an approach.

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