CD155 expression impairs anti-PD1 therapy response in non-small cell lung cancer
Chang Jiang1, Xiaodie Qu2, Li Ma1
1Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Abstract:
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.
Insights
CD155 expression in non-small cell lung cancer (NSCLC) patients correlates with a poorer response to anti-PD1 immunotherapy. Targeting the CD155 pathway alongside PD1/PD-L1 may enhance treatment efficacy.
Area of Science:
- Immunology
- Oncology
- Translational Medicine
Background:
- CD155 is an immune checkpoint protein interacting with TIGIT.
- Inhibition of CD155 presents a novel cancer therapy strategy.
- The impact of CD155 expression on anti-PD1 therapy response in NSCLC remains unclear.
Purpose of the Study:
- To investigate the association between CD155 expression and response to anti-PD1 therapy in non-small cell lung cancer (NSCLC).
- To evaluate the role of TIGIT expression in this context.
- To explore potential therapeutic strategies targeting CD155.
Main Methods:
- Retrospective observational study.
- Immunohistochemistry used to detect CD155 and TIGIT expression in tumor-infiltrated lymphocytes (TILs).
- Analysis of response to anti-PD1 therapy in advanced NSCLC patients.
Main Results:
- CD155-positive NSCLC patients showed significantly worse response rates (ORR) and progression-free survival (PFS) to anti-PD1 therapy compared to CD155-negative patients.
- The negative impact of CD155 was more pronounced in PD-L1-positive patients, including lung adenocarcinoma (LUAC) and lung squamous cell carcinoma (LUSC).
- TIGIT expression did not correlate with anti-PD1 therapeutic effects.
Conclusions:
- CD155 expression attenuates the efficacy of anti-PD1 therapy in NSCLC and is linked to increased progression risk.
- The CD155 pathway represents a potential immunotherapeutic target.
- Combined targeting of CD155/TIGIT and PD1/PD-L1 pathways may improve immunotherapy outcomes.
