Abscopal regression following radiotherapy for adenocarcinoma

Rees, Gwen; Ross, C. M. D.

doi:10.1259/0007-1285-56-661-63

Cited by 87 publications

(54 citation statements)

References 9 publications

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“…He was the first to use the term 'abscopal effect,' where 'abscopal' is derived from the Latin prefix ab, meaning 'away from,' and the Greek word skopos, meaning 'target.' multiple case studies describing an abscopal effect observed after radiotherapy have been published for a variety of malignancies, including lymphoma, papillary adenocarcinoma, melanoma, adenocarcinoma of the esophagus, chronic lymphocytic leukemia and hepatocellular carcinoma (21)(22)(23)(24)(25).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Finally, the clinical observation that best demonstrates the induction of antitumor immunity by radiotherapy is the abscopal effect (ie, a tumor response in a metastasis outside the irradiated field, after treatment of another tumor site) (61)(62)(63)(64)(65). Although it has been reported in multiple tumor types over the years, abscopal effects are infrequent.…”

Section: Radiation Response Of Tumors: the Role Of The Immune Systemmentioning

confidence: 99%

Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift

Formenti

Demaria²

2013

JNCI: Journal of the National Cancer Institute

890

703

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The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.

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“…Originally described by Mole, the abscopal (from the Latin ab and the Greek scopus, away from the target) effect of radiation therapy is a phenomenon by which a primary tumor is irradiated and a response is seen at distant metastatic sites outside of the path of the radiation (96)(97)(98)(99)(100)(101)(102). Our group has generated pre-clinical evidence that it is mediated by the immune system (103)(104)(105).…”

Section: The Abscopal Effect Of Radiotherapymentioning

confidence: 99%

“…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 regression following radiotherapy for adenocarcinoma

Cited by 87 publications

References 9 publications

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

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

Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift

Role of Activin A in Immune Response to Breast Cancer

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