Using scRNA sequencing, Ng et al. compared LN biopsy samples (non-affected vs. tumor-affected) from SCLC patients to study the antitumor role of MHC-I-independent pathways. Despite being PD-1+, γδ T cells were cytotoxic, infiltrated patient samples, and predicted better outcomes with anti-PD-L1 in patients with high levels of γδ T cells. In preclinical models, γδ T cells were as effective as CD8+ T cells in tarlatamab (DLL3–CD3 BiTE)-redirected SCLC killing, while zoledronate sensitized SCLC cells to Vδ2+ T cell-mediated killing and promoted spontaneous γδ T cell-mediated MHC-I-independent SCLC killing that required BTN2A1. bit.ly/4rAAbrS  @WEHI_research