Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer

Yin, Lu; Xue, Jianxin; Li, Rui; Zhou, Lin; Deng, Lei; Chen, Lin; Zhang, Yan; Li, Yanying; Zhang, Xuanwei; Xiu, Weigang; Tong, Ruizhan; Gong, Youling; Huang, Meijuan; Xu, Yong; Zhu, Jiang; Yu, Min; Li, Mengqian; Lan, Jie; Wang, Jin; Mo, Xianming; Wei, Yuquan; Niedermann, Gabriele; Lü, You

doi:10.1016/j.ijrobp.2020.05.002

Cited by 93 publications

(91 citation statements)

References 30 publications

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“…39 This understanding also sheds new light on the abscopal effect observed with predominantly local treatment, such as radiotherapy. 40 Many studies using experimental tumor models have reported abscopal effects, for instance, in pancreatic cancer, 41 malignant melanoma, 42 colon cancer, 43 lung cancer, 44 and breast cancer . 45 The data of our experimental model suggest gas plasma irradiation to mediate an abscopal effect, too.…”

Section: Discussionmentioning

confidence: 99%

Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo

et al. 2020

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“…Since hypofractionated protocols are suggested to be more immunogenic compared to norm-fractionated ones [31], we focused on this radiation scheme which is more and more used in the clinics [32]. In preclinical mouse models, the local irradiation with a dose per fraction of 8-10 Gy delivered in two to three fractions has been shown to mimic a hypofractionated irradiation schedule in humans [24,33,34]. Recent research further supports the hypothesis that combined strategies are superior to induce efficient systemic anti-tumor responses [35,36].…”

Section: Hhp Vaccines Act Systemically But Only On Previously Irradiamentioning

confidence: 99%

Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment

Rückert

Deloch

Frey

et al. 2021

Cancers

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Radiotherapy (RT) is known to have immune-modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti-PD-1 treatment. In abscopal tumor models, we injected mice with B16-F10 melanoma or TS/A mammary tumors. To evaluate the efficiency of RT in combination with HHP vaccines, we locally irradiated only one tumor with 2 × 8 Gy or 3 × 8 Gy. HHP vaccines further retarded the growth of locally irradiated (2 × 8 Gy) tumors. However, HHP vaccination combined with RT failed to induce abscopal anti-tumor immune responses, namely those to non-irradiated tumors, and even partly abrogated those which were induced with RT plus anti-PD-1. In the latter group, the abscopal effects were accompanied by an elevated infiltration of CD8+ T cells, monocytes/macrophages, and dendritic cells. 3 × 8 Gy failed to induce abscopal effects in association with increased expression of immunosuppressive checkpoint molecules compared to 2 × 8 Gy. We conclude that HHP vaccines induce anti-tumor effects, but only if the tumor microenvironment was previously modulated by hypofractionated RT with not too many fractions, but failed to improve RT plus anti-PD-induced abscopal responses that are characterized by distinct immune alterations.

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“…According to some reports, a combination of ICIs and radiation therapy have achieved high rates of local control. 19,20 The case reported here was treated with pembrolizumab after radiation therapy, and a similar anti-tumor effect might be achieved.…”

Section: Discussionmentioning

confidence: 67%

Pembrolizumab‐induced pancytopenia in a patient with squamous cell lung cancer

et al. 2020

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Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune‐related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88‐year‐old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term antitumor efficacy. Key points Significant findings of the study There are several kinds of immune‐related adverse events. We encountered a case of pembrolizumab‐induced pancytopenia with squamous cell lung cancer. What this study adds Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids.

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Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer

Cited by 93 publications

References 30 publications

Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo

Gas plasma irradiation of breast cancers promotes immunogenicity, tumor reduction, and an abscopal effect in vivo

Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment

Pembrolizumab‐induced pancytopenia in a patient with squamous cell lung cancer

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