Radiation Therapy Shows Promise in Overcoming Immunotherapy Resistance in Certain Cancers

Recent research highlights the potential of radiation therapy to enhance the effectiveness of immunotherapy in treating some resistant forms of cancer. Researchers from Johns Hopkins University School of Medicine, in collaboration with the Netherlands Cancer Institute, have found that radiation can activate the immune system to combat tumors that typically do not respond to immunotherapy. This discovery was published in Nature Cancer and focuses on non-small cell lung cancer.

The study involved analyzing the molecular biology of tumors before and after treatment with radiation combined with immunotherapy. The findings demonstrate that radiation can induce a systemic immune response, even in tumors classified as immunologically 'cold' — those with low mutation burden, lacking PD-L1 expression, and involving mutations in pathways like Wnt. After treatment, these tumors showed significant immune activation, including expansion of T cells, suggesting a 'warming up' of the tumor microenvironment.

This immune activation correlates with improved clinical outcomes, indicating potential for using radiation therapy to overcome primary or acquired resistance to immunotherapy. Dr. Valsamo "Elsa" Anagnostou, senior author, emphasized radiation's role in bypassing resistance mechanisms, especially in lung cancers deemed unlikely to respond.

The study also explored the molecular mechanisms behind the abscopal effect — where localized radiation leads to tumor reduction at distant sites through immune system activation. By examining blood and tumor samples from patients undergoing combined therapy or immunotherapy alone, scientists identified specific immune responses associated with better survival. Notably, those with initially 'cold' tumors that 'warmed up' due to radiation exhibited improved outcomes.

Further, the team confirmed that the T cells expanding in patients recognized mutation-specific neoantigens, affirming that the immune response was targeted and effective. Tracking patient outcomes revealed that this combination approach could translate into meaningful benefits in clinical settings.

This research underscores the importance of interdisciplinary collaboration in advancing cancer treatments and opens new avenues for improving immunotherapy response rates in resistant tumors. It also paves the way for incorporating molecular insights into personalized treatment strategies, potentially transforming cancer care.

For more information, see the original study published in Nature Cancer: doi.org/10.1038/s43018-025-01018-w. Source: https://medicalxpress.com/news/2025-07-therapy-immunotherapy-resistance-cancers.html