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(α)-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 αPD1 therapy. The patients with CD155 positive had a significantly worse response to αPD1 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 αPD1 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 αPD1 therapy, posterior-line αPD1 therapy, and αPD1 combination therapy. Furthermore, the expression of TIGIT was not correlated with the therapeutic effect of αPD1. Our pilot study suggests that CD155 expression attenuates the therapeutic effect of αPD1 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.