CD155 expression impairs anti-PD1 therapy response in non-small cell lung cancer

CD155 is an immune checkpoint protein expressed in tumor cells that interacts with its ligand TIGIT, and inhibition of this point presents a new and novel way for cancer therapy. At present, whether the expression of CD155 affects the response to anti(alpha)-PD1 treatment in non-small cell lung cancer (NSCLC) patients is unclear. This observational study characterizes the expression of CD155 in NSCLC patients and its responses to PD1 inhibitors. We retrospectively detected the expression of CD155 and tumor-infiltrated lymphocyte (TIL) TIGIT by immunohistochemistry in advanced NSCLC patients who had received alpha PD1 therapy. The patients with CD155 positive had a significantly worse response to alpha PD1 therapy compared with CD155-negative patients (ORR: 25.6% vs 54.8%, P < 0.01; median PFS: 5.1 vs 7.1 months, HR = 2.322; 95% CI 1.396-3.861, P = 0.001). This effect is more prominent in PD-L1 positive patients. In PD-L1-positive patients, CD155 expression is associated with a poor response to alpha PD1 therapy in both LUAC (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma); meanwhile, the expression of CD155 was associated with a poor response to the first-line alpha PD1 therapy, posterior-line alpha PD1 therapy, and alpha PD1 combination therapy. Furthermore, the expression of TIGIT was not correlated with the therapeutic effect of alpha PD1. Our pilot study suggests that CD155 expression attenuates the therapeutic effect of alpha PD1 therapy and is associated with a higher risk of progression. The CD155 pathway may be a promising immunotherapeutic target and simultaneously targeting CD155/TIGIT and PD1/PD-L1 can improve the effect of immunotherapy. CD155 impairs anti-PD1 therapy response in non-small cell lung cancer. CD155 positive patients had shorter PFS, lower ORR and 6-month response rate.

Automated summary

CD155 expression in non-small cell lung cancer patients affects the response to anti-PD1 therapy, with CD155-positive patients showing a worse therapeutic effect. CD155 is also associated with poor responses in PD-L1 positive patients, across different stages of PD1 therapy.