“Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain clinical study” – LINGain sub study
Dual HER2 blockade with trastuzumab and pertuzumab in the neoadjuvant setting is considered a more robust treatment approach with significant antitumor activity compared to single agent inhibitors. It has been suggested that the mechanism of action of anti-HER2 molecular therapy is T-cell-mediated immune activation.
The presence of tumor-infiltrating lymphocytes (TILs) constitutes a predictive marker of pathologic complete response to neoadjuvant chemotherapy in breast tumors and there seems to exist a relationship between the infiltration of γδ T cells –a subgroup of immune cells that contribute to lymphoid antitumor surveillance– and the prognosis of breast cancer patients. Although largely demonstrated in preclinical studies, there is lack of evidence regarding this phenomenon at the clinical level.
We are very excited to begin the LINGain project -as a sub study of the phase II PHERGain trial- which will identify immunogenicity biomarkers of response or resistance linked to targeted anti-HER2 therapy. We hypothesize that the activation of the different subtypes of γδ T cells in peripheral blood during dual HER2 blockade with trastuzumab and pertuzumab is a signal of immune response, and it could be considered an early marker useful to predict the efficacy for biological therapy in patients with HER2-positive early breast cancer.
We hope to demonstrate the predictive/prognostic impact of γδ T cells in HER2-positive breast cancer in the neoadjuvant setting, so that γδ T cells may help to guide clinicians in future therapy decisions.