New Biomarker Identified: TAA Burden Could Predict Immunotherapy Success in Cancer Patients Lacking Traditional Markers

In our recent study published in Cancer Immunology Research, we identified Tumor-Associated Antigen (TAA) burden as a key biomarker for predicting the success of immune checkpoint blockade (ICB) therapy in cancer patients who lack traditional markers like PD-L1 and tumor mutation burden (TMB). By developing a novel algorithm to quantify TAA burden, we discovered that patients with high TAA burden, especially those with low T-cell exhaustion, showed significantly better responses to ICB therapy. This finding is particularly crucial for patients who are negative for PD-L1 and TMB, offering new hope for those who otherwise have limited access to immunotherapy.

Our research focused on various cancer types, including urothelial carcinoma and head and neck squamous cell carcinoma (HNSC), where we observed that TAA burden could effectively identify patients likely to benefit from ICB, even when other markers do not predict a response. This study challenges the traditional view that TAAs are not associated with ICB response and highlights the potential of TAA burden as a critical tool in personalized cancer immunotherapy. Our study revealed that TAA burden correlates with ICB benefits in PD-L1-negative urothelial carcinoma and head and neck cancer, provided the tumor immune context is non-exhausted. The functionality of TAA-reactive tumor infiltrating lymphocytes (TILs) is highly dependent on the tumor immune microenvironment (TIME). In hot tumors, TILs are often deeply exhausted due to chronic stimulation and an immunosuppressive TME, making them unresponsive to anti-PD1 therapy. In contrast, in cold tumors with a high TAA burden, TAA-reactive TILs remain functional and can be effectively activated by anti-PD1.This challenges previous skepticism about the association between TAAs and ICB response.

The implications of our findings are significant, as they pave the way for more precise and effective use of ICB therapies. By incorporating TAA burden into clinical practice, we can better tailor treatment strategies, potentially improving outcomes for a broader range of cancer patients. Our study also suggests future directions for TAA-based vaccines and other therapeutic approaches that could enhance the efficacy of cancer immunotherapies, particularly in patients who are currently underserved by existing biomarkers.

Reference: Cancer Immunology Research 2024. Read More.