Paradigms on Immunotherapy Combinations with Chemotherapy
Diego Salas-Benito, José L Pérez-Gracia, Mariano Ponz-Sarvisé, María E Rodriguez-Ruiz, Iván Martínez-Forero, Eduardo Castañón, José M López-Picazo, Miguel F Sanmamed, Ignacio Melero
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 immuno-therapy 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.