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Anti-PD-1 resistance is a significant challenge in cancer immunotherapy, limiting the effectiveness of these treatments for many patients.
Mechanisms of resistance come from
Tumor Microenvironment Factors and tumor cell adaptations
Myeloid-derived suppressor cells (MDSCs) play a crucial role in anti-PD-1 resistance. They express CD274 (Programmed death-ligand 1 (PD-L1)), which interacts with CD279 (Programmed cell death protein 1 (PD-1) on T cells, inhibiting cytotoxic T lymphocyte expansion.
Regulatory T cells (Tregs) increase in number during acquired resistance to anti-PD-1/CTLA-4 therapy
One mechanism of anti-PD-1 resistance involves the loss of MHC class I / HLA class I human or human leukocyte antigen (HLA) class I, which are crucial for antigen presentation. This loss impairs the ability of cancer cells to be recognized by the immune system, making them resistant to PD-1 blockade.
see also:
Anti-PD-1 antibodies / PD-1 inhibitors + Fecal Microbiota Transplantation (FMT) & Gastrointestinal Cancers
Gut microbiota & Immune Checkpoint Inhibitors (ICIs)