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 to 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.
Background: Although guidelines recommended to test EGFR/ALK/ROS-1 gene alterations in advanced non-small cell lung cancer (NSCLC) patients before treatment, there is now growing evidence that rare driver genes and mutations also can inform targeted therapy and improve outcomes for this traditionally underrepresented population. This study aimed to describe mutational patterns and linked clinical parameters in a Chinese population-based NSCLC cohort.Methods: This study included patients with pathologically confirmed NSCLC, who were routinely screened for EGFR, KRAS, BRAF, ALK, ROS1, RET, MET, HER2, and PIK3CA mutations by the NMPA approved multi-gene detection kit. The demographic and clinicopathological data, treatment information, clinical outcomes after first-line treatment, as well as nine driver gene mutation statuses and PD-L1 expression level of these patients were retrospectively collected.Results: Finally, 431 patients were enrolled, most patients were male (55.9%), with adenocarcinoma or adenosquamous carcinoma (80.7%) and in stage IV (50.6%). Among all the 431 patients, 61.5% patients were identified with gene mutation including 101 with rare mutation, 164 with 19del or with L858R mutation. Adenocarcinoma patients have a higher mutation rate (73.6%), and the mutations mainly occur in EGFR, KRAS, ALK and HER2. While, the gene mutation characteristics in squamous cell carcinoma patients with were relatively simple, only 2 patients with EGFR 19del and 2 patients with PIK3CA mutation. More PD-L1 expression could detected in patients with rare mutation. The median PFS1 of patients with common mutation (13 months, 95% CI: 9.9-16) was longer than the patients with rare mutation (5 months, 95 % CI: 0-10.5). Conclusions: The clinicopathologic features and clinical treatment status among NSCLC patients with common or rare driver gene mutations were different. The survival of patients with rare mutation was worse than that of patients with common mutation. Therefore, more attention should be paid to the treatment strategy and survival status of patients with rare mutations in clinical practice.
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