Chromosomal Abnormality Scores Pave the Way for Personalized Cancer Immunotherapy

Recent research published in Nature Genetics highlights the potential of tumor chromosomal abnormalities, particularly aneuploidy, as a significant biomarker for predicting how patients respond to immunotherapy. Conducted by scientists at the University of Chicago, the study demonstrates that high levels of chromosomal imbalance in tumors correlate with resistance to immunotherapy across various cancer types. Notably, the research emphasizes the promising strategy of combining radiation therapy with immune checkpoint blockade to overcome this resistance.

Immunotherapy has greatly advanced cancer treatment, yet it remains ineffective in a large proportion of patients—up to 80-90%—underscoring the need for better predictive markers. The team analyzed blood and tissue samples, revealing that tumors exhibiting high aneuploidy tend to evade immune detection, resulting in poorer responses to therapy. Importantly, their findings show that adding radiation therapy can reprogram the tumor microenvironment, potentially reversing immune resistance by eliminating immunosuppressive cells and enhancing immune cell infiltration.

These insights build upon previous studies indicating that chromosomal abnormalities serve as crucial biomarkers for immunotherapy outcomes. By quantifying aneuploidy scores through advanced genomic techniques such as next-generation sequencing, the researchers propose integrating this measure into clinical practice. This approach would complement existing biomarkers like tumor mutational burden (TMB) and PD-L1 expression, especially valuable in cases where TMB is low.

The study advocates for leveraging aneuploidy scoring to personalize treatment plans. This could involve selecting patients more likely to benefit from combined radiation and immunotherapy, leading to more targeted and effective interventions. Moreover, Pitroda’s team is working to embed this biomarker into routine genomic testing platforms, supporting precision oncology efforts.

While targeting chromosomal abnormalities directly remains complex, understanding their role in therapy resistance opens new avenues for drug development, especially for tumors with predictable aneuploidy patterns. Ultimately, tumor aneuploidy emerges as a powerful prognostic and predictive tool, guiding clinicians in optimizing immunotherapy strategies and improving patient outcomes.

Source: https://medicalxpress.com/news/2025-07-chromosomal-abnormality-scores-path-personalized.html