Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature
Open Access
- 1 September 2013
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 19 (17), 4843-4853
- https://doi.org/10.1158/1078-0432.ccr-13-0352
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. This 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 quantitative reverse transcription 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. Clin Cancer Res; 19(17); 4843–53. ©2013 AACR.Keywords
Other Versions
This publication has 45 references indexed in Scilit:
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancerJournal of Experimental & Clinical Cancer Research, 2011
- The Efficacy of Radiotherapy Relies upon Induction of Type I Interferon–Dependent Innate and Adaptive ImmunityCancer Research, 2011
- Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 AntibodyClinical Cancer Research, 2009
- Genome-wide analysis of cancer/testis gene expressionProceedings of the National Academy of Sciences of the United States of America, 2008
- Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cellsImmunological Reviews, 2008
- Immunological aspects of cancer chemotherapyNature Reviews Immunology, 2008
- Cancer immunoediting from immune surveillance to immune escapeImmunology, 2007
- Characterization of a cancer/testis (CT) antigen gene family capable of eliciting humoral response in cancer patientsProceedings of the National Academy of Sciences of the United States of America, 2006
- Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapyThe Journal of Experimental Medicine, 2006