Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report

Okuma, Kae; Yamashita, Hideomi; Niibe, Yuzuru; Hayakawa, Kazushige; Nakagawa, Keiichi

doi:10.1186/1752-1947-5-111

Cited by 94 publications

(66 citation statements)

References 12 publications

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“…1,5,6). In some cases, tumor growth inhibition outside the field of radiation is observed, termed abscopal effect, which suggests the presence of a systemic radiation-induced antitumor immune response (7)(8)(9)(10). However, in general, it is unlikely that radiotherapy alone provides a sufficient antitumor immune response.…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy Combined with the Immunocytokine L19-IL2 Provides Long-lasting Antitumor Effects

Zegers

Rekers

Quaden

et al. 2015

Clinical Cancer Research

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Purpose: Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression.Experimental Design: Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunologic parameters, and treatment toxicity were evaluated after singledose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls.Results: ED-B expression was high, intermediate, and low for C51, LLC, and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8 þ

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Section: Introductionmentioning

confidence: 99%

Radiotherapy Combined with the Immunocytokine L19-IL2 Provides Long-lasting Antitumor Effects

Zegers

Rekers

Quaden

et al. 2015

Clinical Cancer Research

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“…This phenomenon is extremely rare, but when it does occur, its anticancer effects can be dramatic, leading to the disappearance of malignant growths throughout the body. Such success has been described for a variety of malignancies, including melanoma, lymphoma, and lung metastases of hepatocellular carcinoma (1)(2)(3). The mechanism underlying the abscopal effect remains to be clarified, although a variety of underlying biological events may be responsible, particularly those induced by the immune system (4).…”

Section: Introductionmentioning

confidence: 99%

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

et al. 2014

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Abstract. The aim of this study was to assess whether modulated electro-hyperthermia (mEHT) can induce an abscopal effect and thereby enhance the antitumor effects of immunotherapy. We used an intratumoral dendritic cell (DC) injection and mEHT to treat C3H/He mice inoculated with squamous cell carcinoma SCCVII cells in the left leg, and we assessed the whole body antitumor effects. Tumors were examined every two or three days in order to assess growth inhibition. The tumor-draining lymph nodes were removed to enable flow cytometric analysis of CD3 + and CD8 + cells, whereas immunohistochemistry was used to assess CD8, S100 and Foxp3 expression in the tumors. Additionally, GP96 expression in the tumors from the different treatment groups was measured. In the control group, the mean tumor volume was larger than that in other groups. These results indicated that the combination therapy of an intratumoral DC injection and mEHT evoked systemic antitumor activity. A larger number of CD3 + and CD8 + cells were detected by flow cytometric analysis in the DC plus mEHT treatment group. Tumor tissue immunostaining showed that CD8 and S100 were more strongly expressed in the DC plus mEHT treatment group, although Foxp3 expression was much higher in the control group. The GP96 gene expression level in the mEHT group was significantly different from the expression level in the control group. An abscopal effect may be induced by mEHT, and the effect of immunotherapy with DCs was strongly enhanced by the overexpression of GP96. GP96 is thought to be one of the molecules explaining the abscopal effect. Direct intratumoral administration of DCs and mEHT may be a feasible future treatment strategy.

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“…Pre-clinical models are less instructive here, since most models involve radiation to tumors implanted into the subcutaneous tissue. However, when reviewing the clinical reports of abscopal effects, these were observed after irradiation targeting visceral metastases (97)(98)(99)(183)(184)(185)(186)(187)(188).…”

Section: Clinical Approaches: What Have We Learned?mentioning

confidence: 99%

Role of Activin A in Immune Response to Breast Cancer

Vanpouille-Box¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information , 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEDecember PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERNew York University 550 1 st avenue New York, NY 10016-6402 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTIn recent years, progress has been made in the development of immune-based therapy for cancer. Conceptually, these treatment strategies have the potential of harnessing the immune system to combat and eliminate cancer cells. One major obstacle to the success of immunotherapy in both human and animal studies is the development of immunologic tolerance in tumor-bearing hosts. Therefore, the immune system fails to recognize cancer cells as dangerous and actively suppresses antitumor immune responses. Identification of the underlying mechanisms and the critical players that drive tolerance to the tumor is critical to improve the therapeutic efficacy of immunotherapy. Recent data indicate that activin A, a small protein secreted by some immune cells and by breast cancer cells has immune regulatory functions that may play a key role in promoting escape of tumors from immune control. The proposed studies will test the hypothesis that activin A secreted by breast cancer cells plays a key role in suppressing antitumor immunity. The goals are to demonstrate the role of activin A produced by breast cancer cells in tumor growth and metastasis, and the potential therapeutic benefit of blocking activin A to increase the response to radiotherapy. IntroductionOwing to its ability to spread systematically, breast cancer remains a life-threatening tumor. Therefore, efforts in developing new treatment strategies are needed in order to eradicate metastatic breast cancer. In this respect, the activation of the immune system to elicit anti-tumor immune responses represents one of the most promising approaches that have recently demonstrated some success in other diseases. H...

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Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report

Cited by 94 publications

References 12 publications

Radiotherapy Combined with the Immunocytokine L19-IL2 Provides Long-lasting Antitumor Effects

Radiotherapy Combined with the Immunocytokine L19-IL2 Provides Long-lasting Antitumor Effects

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

Role of Activin A in Immune Response to Breast Cancer

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