Changes of systemic immune response after stereotactic ablative radiotherapy (SABR) - first results of a prospective study in early lung cancer patients

Rutkowski, Jacek; Ślebioda, Tomasz Jerzy; Kmieć, Zbigniew; Zaucha, Renata

doi:10.20452/pamw.3997

Cited by 16 publications

(20 citation statements)

References 21 publications

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“…28 Trovo et al characterized cytokine changes following SBRT versus conventional radiation for early stage NSCLC, and found a mean reduction of IL-10 and IL-17 plasma levels, but did not look at individual immune cell subsets. 29 Rutkowski et al studied immune cell types after SBRT and observed an increase in the proportion of total CD8+ T cells, total CD4+ T cells, and CD4+ T cells expressing GATA-3, T-bet or ROR-γt, as well as a decrease in CD4+ Foxp3+ regulatory T cells, 43 however this study did not evaluate NK cells. All of these studies examine the immune phenotype after SBRT to the lung alone.…”

Section: Discussionmentioning

confidence: 86%

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

McGee

Daly

Azghadi

et al. 2018

International Journal of Radiation Oncology*Biology*Physics

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Our data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM3 NK cells, and an increase in activated memory CD4 and CD8 T cells. SAR to nonparenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes that are dependent on the irradiated site.

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Section: Discussionmentioning

confidence: 86%

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

McGee

Daly

Azghadi

et al. 2018

International Journal of Radiation Oncology*Biology*Physics

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“…A prospective study examining resected tumors from early‐stage lung cancer patients reported changes in both CD4 + and CD8 + T cells after stereotactic ablative radiotherapy (SABR), with the detectable expression of GATA‐3, T‐bet and ROR‐γt – transcription factors of Th2, Th1 and Th17 CD4 + T cells, respectively, and a reduction in CD4 + Foxp3 + regulatory T cells (Tregs). This suggests SABR augmented systemic antitumor immune responses by increasing the number of pro‐inflammatory/killer cells – particularly CD4 + and CD8 + T cells 64 . In addition, combining low‐dose total body irradiation (L‐TBI) of 0.1 Gy at a dose rate of 24 cGy min −1 with hypofractionated therapy (HFT) of 8 Gy × 3 at a dose rate of 400 cGy min −1 resulted in greater levels of activated CD8 + T cells in secondary tumors, along with high CD8 + IFN‐γ + T cells and reduced granulocytic MDSC and M2 macrophages.…”

Section: Effects Of Radiotherapy On the Tumor Immune Microenvironmentmentioning

confidence: 98%

“…This suggests SABR augmented systemic antitumor immune responses by increasing the number of pro-inflammatory/killer cellsparticularly CD4 + and CD8 + T cells. 64 In addition, combining low-dose total body irradiation (L-TBI) of 0.1 Gy at a dose rate of 24 cGy min À1 with hypofractionated therapy (HFT) of 8 Gy 9 3 at a dose rate of 400 cGy min À1 resulted in greater levels of activated CD8 + T cells in secondary tumors, along with high CD8 + IFN-c + T cells and reduced granulocytic MDSC and M2 macrophages. To confirm that CD8 + IFN-c + T cells induced by combined L-TBI and HFT contributed to the suppression of tumor growth and metastasis, CD8 + T cells were depletedwhereupon reduced suppressive effects of the combination therapy were observed, suggesting the responses were dependent on CD8 + T cells.…”

Section: Promoting and Inhibiting Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Enhancing the efficacy of immunotherapy using radiotherapy

et al. 2020

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Recent clinical breakthroughs in cancer immunotherapy, especially with immune checkpoint blockade, offer great hope for cancer sufferersand have greatly changed the landscape of cancer treatment. However, whilst many patients achieve clinical responses, others experience minimal benefit or do not respond to immune checkpoint blockade at all. Researchers are therefore exploring multimodal approaches by combining immune checkpoint blockade with conventional cancer therapies to enhance the efficacy of treatment. A growing body of evidence from both preclinical studies and clinical observations indicates that radiotherapy could be a powerful driver to augment the efficacy of immune checkpoint blockade, because of its ability to activate the antitumor immune response and potentially overcome resistance. In this review, we describe how radiotherapy induces DNA damage and apoptosis, generates immunogenic cell death and alters the characteristics of key immune cells in the tumor microenvironment. We also discuss recent preclinical work and clinical trials combining radiotherapy and immune checkpoint blockade in thoracic and other cancers. Finally, we discuss the scheduling of immune checkpoint blockade and radiotherapy, biomarkers predicting responses to combination therapy, and how these novel data may be translated into the clinic.

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“…62 In addition, changes in both CD8 + and CD4 + T cells have been documented in NSCLC following SBRT. 63 The proportion of overall CD8 + T cells and CD4 + T cells as well as activated CD4 + T cells expressing GATA-3, T-bet, and ROR-γt increased following SBRT in patients with NSCLC, whereas the levels of CD4 + FoxP3 + regulatory T cells (Tregs) decreased.…”

Section: Radiation Effects On the Immune Systemmentioning

confidence: 99%

The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules

Arnold

Flynn

Raben

et al. 2018

Cancer�Growth�Metastasis

125

131

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In addition to inducing lethal DNA damage in tumor and stromal cells, radiation can alter the interactions of tumor cells with their microenvironment. Recent technological advances in planning and delivery of external beam radiotherapy have allowed delivery of larger doses per fraction (hypofractionation) while minimizing dose to normal tissues with higher precision. The effects of radiation on the tumor microenvironment vary with dose and fractionation schedule. In this review, we summarize the effects of conventional and hypofractionated radiation regimens on the immune system and tumor stroma. We discuss how these interactions may provide therapeutic benefit in combination with targeted therapies. Understanding the differential effects of radiation dose and fractionation can have implications for choice of combination therapies.

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Changes of systemic immune response after stereotactic ablative radiotherapy (SABR) - first results of a prospective study in early lung cancer patients

Cited by 16 publications

References 21 publications

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

Stereotactic Ablative Radiation Therapy Induces Systemic Differences in Peripheral Blood Immunophenotype Dependent on Irradiated Site

Enhancing the efficacy of immunotherapy using radiotherapy

The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules

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