Radiation therapy and the abscopal effect: a concept comes of age

Ng, John; Dai, Tong

doi:10.21037/atm.2016.01.32

Cited by 63 publications

(55 citation statements)

References 31 publications

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“…This process is likely mediated by the immune system, with dendritic cells, T-regulatory cells and suppressor cells acting as critical mediators (9)(10)(11). Our result may demonstrate that PD1/PD-L1 immunomodulation contributes to this abscopal effect (12). ANTICANCER RESEARCH 37: 2269-2274 (2017) 2272 Figure 4.…”

Section: Discussionmentioning

confidence: 84%

PD-L1 Expression in Patients with Non-small Cell Lung Cancer

Masago

Fujita

Hata

et al. 2017

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Section: Discussionmentioning

confidence: 84%

PD-L1 Expression in Patients with Non-small Cell Lung Cancer

Masago

Fujita

Hata

et al. 2017

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“…Radiation is able to affect change at abscopal sites via its effects on the immune system. At the site of treatment, dead cells release damage-associated molecular patterns (DAMPs), such as ATP, which in turn activate local dendritic cells, increasing antigen presentation (62–63). Radiation can also increase the diversity of presented antigens (64) and localize macrophages to the tumor (65).…”

Section: Discussionmentioning

confidence: 99%

“…For less immunogenic cancers, combining radiation with immunomodulatory molecules may provide the boost needed to see anticancer effects at distant sites. Preclinical data regarding the combination of radiation with IL-2, Flt3-L, TLR ligands (63), and CTLA-4 (67–68) have been published, with promising results. A limited number of studies have looked at treating lung cancer patients with radiation and GM-CSF (69) or ipilimumbab (66), but never before have the combination of anti-PD-1 and irradiation been examined (although Deng et al recently published on the combination of anti-PD-L1 antibody and radiation in the TUBO breast cancer model, 70).…”

Section: Discussionmentioning

confidence: 99%

Decreased Survival After Combining Thoracic Irradiation and an Anti-PD-1 Antibody Correlated With Increased T-cell Infiltration Into Cardiac and Lung Tissues

Myers¹,

Lü²

2017

International Journal of Radiation Oncology*Biology*Physics

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Purpose Lung cancer is the leading cause of cancer-related mortality in the United States. Radiation, a common component of treatment, can cause acute damage to critical organs including the lungs and the heart, but the serious toxicities from radiotherapy alone is relatively rare. A recent addition to the treatment regimen is immunotherapy, such as anti-PD-1 antibody, which blocks the inhibition of activated T cells. Combining anti-PD-1 treatment and thoracic radiation has potential for improving the outcomes of locally advanced lung cancer over traditional chemoradiation regimens, but the effect of combining these therapies on non-malignant lung tissue has not yet been investigated in preclinical models. Materials and Methods 6–8 week old C57Bl/6 mice were treated with either anti-PD-1 antibody or control IgG with or without thoracic radiation (20Gy), and survival was monitored as an end point to determine any potential increase of toxicity from the combination therapy. Immune cell infiltration into the irradiated cardiac and lung tissues was analyzed via flow cytometry and histologically. Results At 21 days post-radiation, 70% of animals in the IgG + radiation group survived, significantly more than the anti-PD-1 + radiation group (36%; p=0.0169). T cell counts were significantly elevated in both cardiac and pulmonary tissues after combination therapy as compared to anti-PD-1 antibody alone (heart: 6.1 vs 22.4, p<0.001; lung 3.4 vs 20.8, p<0.001) or control IgG plus radiation (heart 11.3 vs 22.4, p<0.05; lung 12.2 vs 20.8, p<0.05) in flow cytometric studies. Histologic analysis confirmed this increase in the comparison of anti-PD-1 antibody alone versus antibody plus irradiation (heart: 464 vs 679 cells per field, p<0.001; lung: 780 vs 1109, p<0.001) and control IgG plus radiation or combination therapy (heart: 526 vs 679 cells per field, p<0.001; lung: 848 vs 1109, p<0.05). Conclusions Combining anti-PD-1 antibody and thoracic irradiation results in T cell infiltration into lung and heart tissue and increases mortality in a preclinical model. We conclude that healthy tissue damaged by irradiation is more susceptible to further damage by activated T cells.

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“…In this case, the lingual lobe mass, which was not the target of radiotherapy, received very low dose of radiation (667.8cGy), which supported the notion that abscopal effect was likely mediated by activation of the immune system. 5,6 Postow reported a patient with melanoma had a systemic response to localized radiotherapy combined with immunotherapy with ipilimumab. Golden reported the first abscopal response which is observed after the initial treatment with ipilimumab 7 and fractionated radiotherapy in a patient with chemotherapy-refractory metastatic adenocarcinoma of the lung.…”

Section: Discussionmentioning

confidence: 99%

Abscopal regression following SABR for non-small-cell-lung cancer: A case report

Cong

et al. 2016

Cancer Biology & Therapy

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Out-of-field tumor response, which is also called abscopal effect, bystander effect, or non-target effect, can be regarded as localized irradiation induced systemic antitumorigenic effects, indicating shrinkage of a tumor distant from the irradiated site. Although abscopal effect has been documented in several tumor types, it is a very rare phenomenon which is clinically reported in non-small-cell-lung carcinoma (NSCLC). Herein, we present a rare case of patient with NSCLC with 2 lesions in the upper lobe of left lung who, after receiving stereotactic ablative radiation therapy (SABR) to one of the tumors, had an apparent spontaneous regression of the other mass in the lung, suggestive of a radiation-induced abscopal effect.

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Radiation therapy and the abscopal effect: a concept comes of age

Cited by 63 publications

References 31 publications

PD-L1 Expression in Patients with Non-small Cell Lung Cancer

PD-L1 Expression in Patients with Non-small Cell Lung Cancer

Decreased Survival After Combining Thoracic Irradiation and an Anti-PD-1 Antibody Correlated With Increased T-cell Infiltration Into Cardiac and Lung Tissues

Abscopal regression following SABR for non-small-cell-lung cancer: A case report

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