Abstract 1021P
Background
Our previous research has found an association of long non-coding RNA (lncRNA) pattern with immunotherapy benefit, but the master lncRNAs that contribute to immunotherapy response or resistance and the underlying mechanisms remain largely unknown.
Methods
The 348 bladder cancer patients treated with PD-L1 inhibitor atezolizumab from the phase II IMvigor210 trial were included. Univariate and multivariate Cox regression analyses were conducted to select important lncRNAs. A lncRNA is regarded as a regulator of cytotoxic T lymphocyte (CTL) activity if the effect of CTLs on overall survival (OS) depends on the level of this lncRNA.
Results
We identified eight lncRNAs significantly affecting OS, among which six were associated with longer OS, including LINC00937 (HR 0.67, 95% CI 0.48-0.93), AP000251.1 (HR 0.58, 95% CI 0.36-0.95), SLFNL1.AS1 (HR 0.51, 95% CI 0.32-0.81), ZNF503.AS2 (HR 0.56, 95% CI 0.34-0.92), BVES.AS1 (HR 0.50, 95% CI 0.28-0.87), and SBF2.AS1 (HR 0.53, 95% CI 0.31-0.91). Patients with high LINC00937 expression had higher CTL level than those with low LINC00937 (P<.001), and had a significantly better OS in high CTL versus low CTL (HR 0.53, 95% CI 0.34-0.83). However, no significant difference in OS was observed in high CTL versus low CTL among patients with low LINC00937, indicating a potential role of LINC00937 in initiating CTL activity. Such effect was also shown with AP000251.1. SLFNL1.AS1 and ZNF503.AS2 were not shown to affect CTL, but were associated with high tumor mutation burden (P=.02 and .03, respectively). Patients with high PCAT1 expression had inferior OS (HR 2.14, 95% CI 1.25-3.64), lower CTL infiltration (P<.001), and lower PD-L1 expression (P<.001) compared with those with low PCAT1 expression, suggesting an immunosuppressive role of PCAT1 in tumor microenvironment.
Conclusions
This study identified essential lncRNAs that positively or negatively play dominant role affecting immunotherapy efficacy via regulating T-cell infiltration and activity or tumor antigenicity. Future research should attempt to improve immunotherapy benefit by modulating these lncRNAs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
A. Li.
Funding
National Students’ Innovation and Entrepreneurship training program (Grant n. 201910571001); Special Funds for the Cultivation of Guangdong College Students’ Scientific and Technological Innovation (Grant n. pdjh2019A0212); Guangdong Medical University College Students’ Innovation Experiment Project (Grant n. ZZZF001).
Disclosure
All authors have declared no conflicts of interest.