Why Keytruda Stops Working: Overcoming Tumor Microenvironment Immunotherapy Resistance
Originally compiled for translational precision oncology tracking. References to clinical registries provided inline. Pembrolizumab (Keytruda) has fundamentally shifted the treatment paradigm for advanced malignancies by blocking the Programmed Death-1 (PD-1) receptor. However, clinical data shows that up to 60–70% of patients experience either primary resistance (lack of initial response) or adaptive secondary resistance (progression after a period of response). Accumulating clinical evidence points to the Tumor Microenvironment (TME) as the principal driver of this therapeutic failure. This review synthesizes the cell-extrinsic and cell-intrinsic mechanisms within the TME that neutralize cytotoxic T-cell activity and maps out strategic metabolic and microenvironmental interventions to restore anti-PD-1 sensitivity. 1. Introduction: The Mechanism of Immune Checkpoint Blockage (ICB) The therapeutic rationale behind pembrolizumab relies on a simple premise: unmask...