PD-L1 Levels Modify Aspirin Effect On CRC Survival

Tumoural expression of programmed cell death ligand 1 could help identify patients with colorectal cancer who may benefit from aspirin use after cancer diagnosis

medwireNews: The association between postdiagnosis aspirin use and improved survival in patients with colorectal cancer (CRC) is restricted to those with tumours that have low levels of programmed cell death ligand 1 (PD-L1), findings indicate.

Emerging evidence suggests that aspirin (acetylsalicylic acid) can reverse tumour immune evasion by blocking prostaglandin E2, which together with immune checkpoint blockade can stimulate a T cell-mediated antitumour response, implying that "activated status of immune checkpoint in cells within the tumor microenvironment may confer resistance to aspirin", the study authors explain.

And indeed, they found a significant interaction between postdiagnosis aspirin use and tumour PD-L1 (also known as CD274) expression, such that, after accounting for confounders, aspirin use was significantly associated with extended CRC-specific survival in patients who harboured tumours with low PD-L1 levels (adjusted hazard ratio [HR]=0.16), but not in those with high PD-L1 tumours (HR=1.01).

The results were similar for overall survival, with aspirin use significantly linked to a reduced risk of death only in patients with low tumoural PD-L1 expression (HR=0.38), report Shuji Ogino, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-authors.

“Our findings supporting the differential effects of aspirin according to immune checkpoint status underscore the potential of dual prostaglandin inhibition and immune checkpoint blockade as a combination immunotherapy strategy to further improve clinical outcome”, they write in the Journal of Clinical Oncology.

The team continues: “Given [the] growing popularity of immune checkpoint inhibitors for cancer treatment, our findings, if validated, may have considerable clinical implications for adjuvant aspirin use in the era of immunotherapy.”

The study included 617 CRC patients drawn from two US cohorts – the Nurses’ Health Study and the Health Professionals Follow-Up Study – for whom postdiagnosis aspirin use and tumour PD-L1 expression data were available. Aspirin users were those who took the non-steroidal anti-inflammatory drug at least twice a week, whereas nonusers were those who took the drug once a week or not at all.

The participants were followed up for a median of 11.5 years, during which there were 325 all-cause deaths, of which 118 were attributable to CRC.

Reference

Hamada T, Cao Y, Qian ZR, et al. Aspirin use and colorectal cancer survival according to tumor CD274 (programmed cell death 1 ligand 1) expression status. J Clin Oncol; Advance online publication 13 April 2017. doi:10.1200/JCO.2016.70.7547

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