Paradigms on Immunotherapy Combinations with Chemotherapy.
Diego Salas-BenitoJose-Luis Perez-GraciaMariano Ponz-SarviséMaría E Rodriguez-RuizIván Martínez-ForeroEduardo CastañónJosé M López-PicazoMiguel F SanmamedIgnacio MeleroPublished in: Cancer discovery (2021)
Checkpoint inhibitors are being added to standard-of-care chemotherapy in multiple clinical trials. Success has been reported in non-small and small cell lung carcinomas and urothelial, head and neck, gastric, and esophageal cancers, and promising results are already available in triple-negative breast and pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor cell death, antiangiogenesis, selective depletion of myeloid immunosuppressive cells, and lymphopenia, which reduces regulatory T cells and makes room for proliferation of effector T cells. However, chemotherapy regimens have not been optimized for such combinations, perhaps explaining some recent clinical trial disappointments. Approaches to make the most of chemoimmunotherapy include neoadjuvant and adjuvant schemes.Significance: Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management. Evidence in phase III clinical trials already supports combinations of immunotherapy with standard-of-care chemotherapy for a number of malignant diseases. This review focuses on such evidence and provides an overview of the potential synergistic mechanisms of action and the opportunities to optimize chemoimmunotherapy regimens.
Keyphrases
- clinical trial
- regulatory t cells
- phase iii
- locally advanced
- phase ii
- dendritic cells
- open label
- cell death
- papillary thyroid
- healthcare
- rectal cancer
- palliative care
- double blind
- squamous cell carcinoma
- study protocol
- squamous cell
- cell cycle arrest
- high grade
- induced apoptosis
- radiation therapy
- risk assessment
- early stage
- quality improvement
- signaling pathway
- stem cells
- dna damage
- acute myeloid leukemia
- lymph node metastasis
- childhood cancer
- climate change
- mesenchymal stem cells