Powles RL, et al. - Researchers investigated the influence of using the T-cell β chain variable genes on the potential association of immune gene signatures with response to dual HER2 blockade. They performed this biomarker study of data from the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALTTO) trial. Using high levels of a T-cell receptor β variable region (TRBV) metagene consisting of 3 individual TRBV genes, they identified a subgroup of patients who respond poorly to single HER2 blockade treatments, irrespective of overall immune signature expression. These patients, however, experienced a significant benefit from dual anti-HER2 blockade. Findings thereby suggest an independent predictive value of direct measurements of TRBV use for response to dual HER2-targeted therapy.