Tumor beta2-microglobulin and HLA-A expression is increased by immunotherapy and can predict response to CIT in association with other biomarkers

• DOI: 10.3389/fimmu.2024.1285049
• Publication Date: 2024-02-22T05:52:59Z
• Authors: Bernhard Reis; Jan Attig; Sebastian Dziadek; Nico Graefe; Astrid Heller; Natascha Rieder; Bruno Gomes
• Keywords: Beta-2 microglobulin

Background Downregulation of MHC class I expression and/or defects in the antigen presentation pathways are commonly reported human cancers. Numerous studies previously have explored extensively molecular mechanisms that underlie HLA-class and Beta2-Microglobulin (B2M) downregulation. However, techniques presently available to detect proteins lack robustness, specificity sensitivity needed for systematic integration analysis clinical trials. Furthermore, dynamics B2M not been comprehensively studied as a potential biomarker immunotherapy. Methods Using novel, validated, immunohistochemistry (IHC)-based methods quantifying HLA-A tumor samples from diverse cancer types, we determined loss 336 archived, primary specimens 329 biopsies metastatic patients collected during Roche-sponsored Phase 1 trials investigating novel immunotherapy candidates monotherapy or combination with CPI. Results Up 56% cases were noted investigated types. The frequency was dependent on indication stage disease revealed heterogeneous patterns across patients. increased lesions compared tumors, indicating selection low clones refractory cells. High on-treatment correlated successful outcome (RECIST), while high baseline did not. A treatment-induced increase most levels at baseline. triple B2M, CD8 PDL1 strongly improved response prediction Conclusion Our results indicate occurs frequently tumors is reversed instances following which supports conclusion dominant resistance mechanism CPI treatment. This investigation reveals highly dynamic affected by indication, status, immunophenotype Baseline may be utility constituent panel used selecting