In situ Tumor Ablation with Radiation Therapy: Its Effect on the Tumor Microenvironment and Anti-tumor Immunity

McBride, William H.; Schaue, Dörthe

doi:10.1007/978-94-007-4694-7_6

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…It has been suggested that the high efficacy of SBRT and SRS is due to their ability to stimulate antitumor immunity (33–35). However, it is unlikely that the massive secondary cell death which occurs within 2 to 3 days after an exposure to high-dose irradiation is caused by elevation of antitumor immune response, because a significant increase in tumor-specific immune systems as a result of high-dose irradiation of tumors takes longer than at least 1 week (34).…”

Section: Discussionmentioning

confidence: 99%

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

Song

Lee

Griffin

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

132

103

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Summary In experimental mouse tumors, high-dose irradiation in a single fraction caused progressive increase in tumor cell death in 2 to 5 days. Such delayed tumor cell deaths appeared to be due to radiation-induced deterioration of intratumor microenvironment characterized by profound reduction of blood perfusion and increase in hypoxia. Similar secondary and indirect cell death may play an important role in clinical stereotactic body radiation therapy and stereotactic radiation surgery. Purpose The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo—in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

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Section: Discussionmentioning

confidence: 99%

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

Song

Lee

Griffin

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

132

103

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“…Several modes of EBRT were developed such as stereotactic radiotherapy (SRT), stereotactic body radiation therapy (SBRT), its extension stereotactic ablative radiotherapy (SABR), and lately, intensity modulated radiation therapy (IMRT) (29).…”

Section: Radiationmentioning

confidence: 99%

Tumor abolition and antitumor immunostimulation by physico-chemical tumor nbsp ablation

Keisari

2017

Front Biosci

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Tumor ablation by thermal, chemical and radiological sources has received substantial attention for the treatment of many localized malignancies. The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume through the application of energy or chemicals. Methods such as radiotherapy, chemical and biological ablation, photodynamic therapy, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and electric-based ablation have been developed for focal malignancies. In recent years a large volume of data emerged on the effect of tumor destruction (ablation) on inflammatory and immune components resulting in systemic anti-tumor reactions. It is evident that tumor ablation can involve tumor antigen release, cross presentation and the release of DAMPS and make the tumor its own cellular vaccine. Tumor tissue destruction by ablation may stimulate antigen-specific cellular immunity engendered by an inflammatory milieu. Dendritic cells (DCs) attracted to this microenvironment, will undergo maturation after internalizing cellular debris containing tumor antigens and will be exposed to damage associated molecular pattern (DAMP). Mature DCs can mediate antigen-specific cellular immunity via presentation of processed antigens to T cells. The immunomodulatory properties, exhibited by ablation could portend a future collaboration with immunotherapeutic measures. In this review are summarized and discuss the preclinical and clinical studies pertinent to the phenomena of stimulation of specific anti-tumor immunity by various ablation modalities and the immunology related measures used to boost this response.

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“…It has been reported that high dose hypo-fractionated irradiation promotes anti-tumor immunity [ 37 38 39 40 ], whereas multi-fractionated radiotherapy with a small dose per fraction suppresses immune competency of the host. Finkelstein et al [ 37 ] attributed the increase in anti-tumor responses by SBRT to elevation of the expression of immune-modulator molecules such as histocompatibility complex, adhesion molecules, heat shock proteins, inflammation mediators, immunomodulating cytokines, and death receptors on the surface of tumor cells.…”

Section: Indirect Tumor Cell Death Due To Immune Response In Sbrt Andmentioning

confidence: 99%

Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery

et al. 2015

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Despite the increasing use of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS) in recent years, the biological base of these high-dose hypo-fractionated radiotherapy modalities has been elusive. Given that most human tumors contain radioresistant hypoxic tumor cells, the radiobiological principles for the conventional multiple-fractionated radiotherapy cannot account for the high efficacy of SBRT and SRS. Recent emerging evidence strongly indicates that SBRT and SRS not only directly kill tumor cells, but also destroy the tumor vascular beds, thereby deteriorating intratumor microenvironment leading to indirect tumor cell death. Furthermore, indications are that the massive release of tumor antigens from the tumor cells directly and indirectly killed by SBRT and SRS stimulate anti-tumor immunity, thereby suppressing recurrence and metastatic tumor growth. The reoxygenation, repair, repopulation, and redistribution, which are important components in the response of tumors to conventional fractionated radiotherapy, play relatively little role in SBRT and SRS. The linear-quadratic model, which accounts for only direct cell death has been suggested to overestimate the cell death by high dose per fraction irradiation. However, the model may in some clinical cases incidentally do not overestimate total cell death because high-dose irradiation causes additional cell death through indirect mechanisms. For the improvement of the efficacy of SBRT and SRS, further investigation is warranted to gain detailed insights into the mechanisms underlying the SBRT and SRS.

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In situ Tumor Ablation with Radiation Therapy: Its Effect on the Tumor Microenvironment and Anti-tumor Immunity

Cited by 5 publications

References 55 publications

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

Tumor abolition and antitumor immunostimulation by physico-chemical tumor nbsp ablation

Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery

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