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Radiotherapy of human sarcoma promotes an intratumoral immune effector signature


Sharma, Anu; Bode, Beata; Moch, Holger; Okoniewski, Michal; Knuth, Alexander; von Boehmer, Lotta; van den Broek, Maries (2013). Radiotherapy of human sarcoma promotes an intratumoral immune effector signature. Clinical Cancer Research, 19(17):4843-4853.

Abstract

PURPOSE: The tumor immune microenvironment plays a crucial role in the development and progression of cancer. Sarcomas are a group of heterogeneous soft tissue malignancies that are often treated with radiotherapy as a part of the treatment concept. There is increasing evidence that radiotherapy leads to alterations in the tumor microenvironment, particularly with respect to the immune infiltrate. The present study has been carried out to develop a better understanding of such changes following radiotherapy.
EXPERIMENTAL DESIGN: We retrospectively analyzed the expression of 35 immune response-related genes by qRT-PCR analysis and immunohistochemistry on paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients before and after radiotherapy.
RESULTS: We observed that radiotherapy results in a significant upregulation of several immune effectors and cancer-testis antigens and a concomitant downregulation of immune suppressors, indicating that radiotherapy may support the immune defense in sarcomas.
CONCLUSIONS: These novel findings may have implications for the design of therapeutic regimens which exploite the immune system in sarcoma patients by combining standard radiotherapy with immunotherapeutic strategies.

Abstract

PURPOSE: The tumor immune microenvironment plays a crucial role in the development and progression of cancer. Sarcomas are a group of heterogeneous soft tissue malignancies that are often treated with radiotherapy as a part of the treatment concept. There is increasing evidence that radiotherapy leads to alterations in the tumor microenvironment, particularly with respect to the immune infiltrate. The present study has been carried out to develop a better understanding of such changes following radiotherapy.
EXPERIMENTAL DESIGN: We retrospectively analyzed the expression of 35 immune response-related genes by qRT-PCR analysis and immunohistochemistry on paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients before and after radiotherapy.
RESULTS: We observed that radiotherapy results in a significant upregulation of several immune effectors and cancer-testis antigens and a concomitant downregulation of immune suppressors, indicating that radiotherapy may support the immune defense in sarcomas.
CONCLUSIONS: These novel findings may have implications for the design of therapeutic regimens which exploite the immune system in sarcoma patients by combining standard radiotherapy with immunotherapeutic strategies.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:16 Aug 2013 07:24
Last Modified:17 Feb 2018 06:10
Publisher:American Association for Cancer Research
ISSN:1078-0432
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1158/1078-0432.CCR-13-0352
PubMed ID:23861514

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