Radiation and Immune Checkpoint Blockade: From Bench to Clinic

Shabason, Jacob E.; Minn, Andy J.

doi:10.1016/j.semradonc.2017.03.002

Cited by 40 publications

(30 citation statements)

References 60 publications

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“…Abscopal effects after extended alternate weekday schedules fractionation preclinically. Despite this caveat, our observations could nevertheless be important for the planning of clinical trials and the clinical implementation of RT/ICB combinations (5,6,45). However, more studies are needed to further elucidate the consequences of repeated tumor irradiation and to clarify to what extent regional lymph nodes should be preserved to guarantee optimal local and abscopal efficacy with hRT/ICB combinations.…”

Section: = Volume 101 Number 1 2018mentioning

confidence: 92%

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Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response

Zhang

Niedermann

2018

International Journal of Radiation Oncology*Biology*Physics

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Our data suggest that combination therapy with hRT schedules extending into the period during which treatment-induced T cells infiltrate the irradiated tumor can provoke local and systemic antitumor effects similar to those with therapy using shorter schedules, if the regional lymph nodes supply sufficient tumor-specific T cells. This has implications for planning clinical RT/immune checkpoint blockade trials.

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Section: = Volume 101 Number 1 2018mentioning

confidence: 92%

“…It can thus enhance the numbers and function of tumor-specific T cells (4). However, the optimal radiation dose and fractionation for the stimulation of T-cell responses to enhance local and abscopal tumor control in combination with ICB are still under investigation (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response

Zhang

Niedermann

2018

International Journal of Radiation Oncology*Biology*Physics

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“…Radiotherapy is generally applied to the cancerous tumor for its cytotoxicity. However, radiotherapy could not only cause damage to cancer cells, but also leading to immunologic cells death indiscriminately [35,36].…”

Section: Discussionmentioning

confidence: 99%

Immune Cell Infiltration in Bladder Cancer

Liu

et al. 2019

Preprint

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Background Bladder cancer is one of the most common malignant diseases with high recurrence rates worldwide. Although immunotherapy has been applied in bladder cancer for a long period of time, the tumor-infiltrating immune cells (TIICs) in bladder cancer has not been systematical investigated. Methods CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs), was applied to calculate the TIICs fraction proportion in normal bladder tissues and in bladder cancer tissues with the TCGA data. Results compared to normal bladder tissue, B cells naïve, T cells CD4 memory resting and Mast cells resting fractions proportion decreased, and NK resting, macrophages M0 and macrophages M1 increased. In BLCAs tissue, pro-tumorigenic related immune cells were negatively correlated with anti-tumor immune cells. New tumor with locoregional had high fraction proportion of macrophages M0 and macrophages M1. Dendritic cells activated, Monocytes, macrophages M1, Tregs and T cells follicular helper significantly increased in low grade BLCAs. Tregs had a high proportion in BLCAs patients accepted low radiation dose. Conclusions This study indicates that macrophages M2 and Tregs could be the promising immunotherapy targets combined radiotherapy in BLCAs. The result provides valuable information to understand the immunity status in BLCAs.

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“…However, recent observations in melanoma patients have shown that anti-PD1 therapy can enhance local response to radiotherapy and promote abscopal effects with tumor regression at unirradiated sites [17]. Preclinical data and early clinical observations supporting synergy between immune checkpoint blockade and radiotherapy across multiple tumor types have been recently reviewed [18, 19]. …”

Section: Discussionmentioning

confidence: 99%

Complete response of mediastinal clear cell sarcoma to pembrolizumab with radiotherapy

2017

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BackgroundClear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS.Case presentationWe report the first complete clinical response of a bulky chest wall recurrence of mediastinal CCS in a young woman to anti-PD1 checkpoint blockade with pembrolizumab combined with standard fractionation radiotherapy to enhance regional control and potentially boost the systemic immune response. The treatment was well tolerated with grade 2 skin toxicity within the range expected with radiation alone. Significant reduction in tumor bulk occurred after only 2 radiation fractions and complete response was achieved at 50 Gray.ConclusionThe complete clinical response observed in our patient suggests synergy between concurrent radiotherapy and PD1 blockade in CCS. This case and the striking parallels between CCS and melanoma indicate the need for prospective trials of immune checkpoint blockade combined with radiotherapy in this rare malignancy.

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Radiation and Immune Checkpoint Blockade: From Bench to Clinic

Cited by 40 publications

References 60 publications

Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response

Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response

Immune Cell Infiltration in Bladder Cancer

Complete response of mediastinal clear cell sarcoma to pembrolizumab with radiotherapy

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