Abstract 1700P
Background
Radiotherapy (RT) is broadly used for cancer treatment, including early breast (eBRCA) and rectal cancers (RC). However, many components of the tumor microenvironment (TME) contribute to RT resistance. RT induces cancer cell death resulting in tumor antigen release that triggers the recruitment of a variety of immune cells that can act either stimulatory or suppressive on anti-tumor immunity. A deeper understanding of the immune suppressive components of anti-tumor immunity is integral to discover novel treatments to improve RT effectiveness. In this study, RT induced transcriptional changes were identified that associate with cellular consequences that may promote radio-resistance. Moreover, the delineation of tumor-specific changes can help selecting patients undergoing RT that are likely to have tumor recurrence.
Methods
Datasets of patients with eBRCA (Horton 2015) and RC (Petty 2009) that received single-dose RT were analyzed. Gene signatures of immune activation and suppression were summarized for each patient as an average of the standard score and evaluated at the baseline and after RT. Fractions of immune cell populations were estimated by cell type deconvolution using xCell (Aran 2017) and compared pre and post RT.
Results
Evaluation of gene signatures of immune activation (inflammatory response, T-cell inflammation) and immune suppression (M2 macrophages, TGF-b signaling) in eBRCA and RC patients showed a consistent increase in pre compared to post RT. The comparison of score fold-change (pre-post RT) showed a stronger increase of the signatures in RC compared to eBRCA, with similar change for the TGF-b signaling score. Cell type deconvolution analysis showed that M1 and M2 macrophages and cancer-associated fibroblasts increase after RT in both tumor types, while NK T cells decrease. The main differences were found in neutrophils and regulatory T cells that have opposite trends in the two tumor types.
Conclusions
The results showed an overall increase of immune activation and suppression genes after RT, more pronounced in RC compared to eBRCA patients. Moreover, the TME of RC showed a more immune-suppressive profile with an increase of regulatory T cells in addition to M2 macrophages.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Idorsia Pharmaceutical Ltd.
Funding
Idorsia Pharmaceutical Ltd.
Disclosure
All authors have declared no conflicts of interest.