| Popis: |
SummaryαβT cells engineered to express a defined γδTCR (TEG) to attack cancer cells have shown great promise when using a γ9δ2TCR to redirect αβT cells (1–9). Reports by us (1–9) and recent reports by others (10, 11) support the key role of the γ9δ2TCR in cancer recognition. We further emphasized the crucial role of the δTCR chain and that differences in CDR3 sequences of the δTCR chain modulates functional avidity of TEGs (2, 8). We and others demonstrated that also δ2 negative γδTCRs are able to redirect αβT cells towards different tumor cell lines (12–15). However, some studies suggest that δ2 negative γδTCRs play a minor role in the tumor recognition by δ2 negative γδT cells (16, 17). In addition for both modes of action for tumor-recognition, δ2 negative γδTCR-dependent and -independent, it has been suggested that CMV infection is not only a major driver of δ2 negative γδT cell expansion (18) but also induces tumor-cross reactive δ2 negative γδT cells (19–21). Therefore, we aimed to systematically explore frequencies of tumor reactive δ2 negative γδT cells in naïve repertoires (cord blood) and patients with or without CMV infection and examined the potential role the parental δ2 negative γδTCR in anti-tumor reactivity of selected clones. We observed that approximately 30% of all tested clones were tumor-reactive, though no differences were observed between different sources. Surprisingly, none of the so far tested γδTCR did mediate strong anti-tumor reactivity of the parental clones. Though numbers of tested TCR sequences are still low, our data imply that tumor-reactivity of δ2 negative γδT cells is frequently not mediated by the δ2 negative γδTCR alone. |
