Tumor-specific major histocompatibility-II expression predicts pathological complete response to atezolizumab combined to chemotherapy in triple-negative breast cancer

Balko, Justin M.Justin M.BalkoLicata, LucaLucaLicataWang, Xiao QianXiao QianWangDugo, MatteoMatteoDugoCHIUN-SHENG HUANGEgle, DanielDanielEgleBermejo, BegoñaBegoñaBermejoZamagni, ClaudioClaudioZamagniThill, MarcMarcThillAnton, AntonioAntonioAntonRusso, StefaniaStefaniaRussoSevillano, ElenaElenaSevillanoCiruelos, Eva MariaEva MariaCiruelosGreil, RichardRichardGreilSemiglazov, VladimirVladimirSemiglazovColleoni, MarcoMarcoColleoniKelly, Catherine M.Catherine M.KellyMariani, GabriellaGabriellaMarianiDel Mastro, LuciaLuciaDel MastroZambelli, StefaniaStefaniaZambelliViale, GiuliaGiuliaVialeCallari, MaurizioMaurizioCallariViale, GiuseppeGiuseppeVialePusztai, LajosLajosPusztaiGianni, LucaLucaGianniAli, H. RazaH. RazaAliBianchini, GiampaoloGiampaoloBianchini2025-12-162025-12-162025-09-29https://scholars.lib.ntu.edu.tw/handle/123456789/734674Adding immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes in early-stage triple-negative breast cancer (TNBC), but a fraction of patients derive benefit. Tumor-specific MHC-II (tsMHC-II) expression has been shown to be a predictive biomarker of pathological complete response (pCR) to neoadjuvant chemo-immunotherapy in early-stage TNBC. We performed biomarker analysis of the phase III NeoTRIP trial where patients were randomized to neoadjuvant carboplatin and nab-paclitaxel±atezolizumab. Imaging mass cytometry was used to assess tsMHC-II expression in tumor samples. TsMHC-II positivity was predefined as ≥5% of tumor cells expressing MHC-II, and at an 80th percentile exploratory cutoff. TsMHC-II positivity was associated with a higher pCR rate in the atezolizumab arm (OR:2.58; P = 0.016), but not in the chemotherapy-only arm (OR:1.37; P = 0.34) and these results were stronger using the exploratory cutoff. TsMHC-II expression is associated with improved response to neoadjuvant chemo-immunotherapy in early TNBC and could represent a clinically useful predictive biomarker for treatment personalization.entrue[SDGs]SDG3Tumor-specific major histocompatibility-II expression predicts pathological complete response to atezolizumab combined to chemotherapy in triple-negative breast cancerjournal article10.1038/s41523-025-00828-6410227792-s2.0-105017645295