Although immunotherapy has revolutionized the treatment of cancer, the translation of immunotherapy-radiotherapy (IT-RT) combinations into the clinic has proven challenging. While radiotherapy can be immuno-stimulatory, it also is known to have several immuno-suppressive properties that may be responsible for difficulty in clinical translation. To this end, the past decade has revealed mounting evidence that various germline mutations, somatic alterations and other tumor-intrinsic molecular features influence the immune contexture of the tumor microenvironment (TME) and thus the potential to modulate the interaction between immunotherapy and radiotherapy. In parallel, molecular-genetic tumor profiling and next-generation sequencing (NGS) are now standard-of-care across a spectrum of malignancies and are increasingly used for prognostication, refinement of treatment selection and monitoring of treatment response. This activity reviews emerging molecular profiles of tumors that influence the interaction of radiotherapy with immunotherapy. In the era of personalized medicine, radiation oncologists should be familiar with immuno-molecular-genomic tumor profiling and how these assays and biomarkers may help identify subgroups of patients that are most likely to benefit from IT-RT combination strategies and help design future trials for potential responders.

Topics:

1. Biologically-Guided Approaches to Address Intrinsic Resistance to IT-RT Combinations
   Yvonne Marie Mowery, MD, PhD, BS 
2. The T cell-inflamed Tumor Microenvironment as a Conceptual Model for Phenotype Adapted Radio-immunotherapy
   Jason J. Luke, MD, FACP
3. Tumor Aneuploidy as a Novel Predictor of Response to Immunotherapy in Combination with Radiation Therapy
   Sean P. Pitroda, MD
4. A Precision Approach to Radiation-Immunotherapy Combinations
   Nadeem Riaz, MD, MSc. 
5. Summary, Conclusions and Q&A
   Ariel E. Marciscano, MD - Moderator
   Full Panel

This activity is available from July 8, 2025, through 11:59 p.m. Eastern time on July 7, 2027. 

The content was originally presented and recorded at the 2024 ASTRO Annual Meeting.