- Aspirin use appears to improve survival post diagnosis in colorectal cancers with certain genetic mutations
- Immune check point inhibitors against the PDCD1 (programmed cell death 1, PD-1) to CD274 (PDCD1 ligand, PD-1) axis have shown exciting clinical benefits in the treatment of refractory cancer.
- Aspirin appears to have a synergistic effect with new immune check point blockade therapies.
The U.S. Food and Drug Administration (FDA) has approved the anti PDCD1 (PD-1) antibody pembrolizumab for the treatment of solid tumours that have high-level microsatellite instability (MSI) or mismatch repair deficiency. This has been seen as an exciting development in cancer therapy as it is the first anticancer agent license based on a tumour biomarker rather than the actual primary cancer site.
High- level MSI is often present in colorectal cancer which may be why immune check point blockade has helped to improve survival in this cancer type. Unfortunately not all MSI-high colorectal cancers respond to immunotherapy. There are many complexities to individual colorectal cancers which are influenced by lifestyle factors, the microbiome and host cells which are thought to result in unique genetic and epigenetic aberrations and a distinct microenvironment. Predictive factors for immune response are therefore required.
Aspirin may reduce colorectal cancer mortality by inhibition of PTGS2 and prostaglandin E2 (PGE2) synthesis. In addition aspirin appears to have immune enhancing effects on the adaptive and innate immune response
These effects seen with aspirin appear to be influenced by the genetic makeup of the cancer. Colorectal cancer with lower-level CD274 (PD-L1) expression appear to benefit from better post diagnosis aspirin use than those with higher-level CD274 expression.
Activation of the CD274-PDCD1 immune checkpoint pathway may result in resistance to aspirin therapy in colorectal cancer treatment. This may be overcome with the use of immune checkpoint blockade therapies. Immune check point therapy and aspirin may work in a synergistic manner to control the progression of colorectal cancer.
For further information see: Hamada T, Giannakis M and Ogino S Aspirin in the era of immunotherapy Oncotarget. 2017 Sept 26: 8(43):73370-73371.