Characterization of Tumor-Infiltrating γδ TCR Repertoires in Human Solid Tumors Using a Low-Input, Sorting-Free Approach

γδ T cells play a crucial role in tumor immunity, yet their tumor-infiltrating TCR-repertoire remains poorly characterized across different cancer types. Additionally, the relationship between γδ TCR repertoires in the blood and tumor compartments remains largely unexplored, limiting our understanding on γδ T cell trafficking, tumor-specific responses, and their therapeutic potential. A major challenge in studying the γδ TCR repertoire in human solid tumors is the low abundance of γδ T cells in the tumor microenvironment. Here, we describe a low-cell-input method that enables direct γδ TCR characterization from bulk tumor samples without the need for cell sorting or enrichment. This approach allows efficient analysis despite limited cellular material, overcomes technical barriers associated with γδ TCR amplification in tumors and provides a more comprehensive view of γδ T cell diversity across different malignancies, offering new insights into their role in cancer immunity.