Evaluation of the clinical and radiological features of advanced stage and metastatic non-small cell lung cancer patients with nivolumab treatment and the effects of LAG-3 and CD-155 expressions on treatment response and survival

Immune checkpoint inhibitors (ICIs) are widely used in non-small cell lung cancer (NSCLC). Although the most commonly used biomarker in predicting treatment response is Programmed Cell Death Ligand-1 (PD-L1), it is known that it is insufficient on its own, and the search for new biomarkers continues. LAG-3 (Lymphocyte Activation Gene-3) and CD-155 (Cluster of Differentiation-55) inhibit antitumor immunity by interacting with various receptors. Clinical data has been collected from 78 metastatic NSCLC patients who used nivolumab due to progression after chemotherapy. LAG-3 expression levels in tumor-infiltrating lymphocytes (TIL) and stromal lymphocytes (33 patients) and cytoplasmic and membranous CD-155 expression levels in tumor cells (61 patients) were evaluated by immunohistochemistry (IHC) and the relationship of these expressions with overall survival (OS) and treatment response have been examined. The median OS of all patients was 8.7 months (95% CI: 5.1-12.3). There was no statistically significant difference between CD-155 and LAG-3 expression and OS, progression-free survival, and treatment response rates [OS was 6.4 months (95% CI: 4.9-7.8) in the group with high CD-155 expression, 11.3 months (95% CI: 6.9-15.8) in the non-high group (p=0.53); LAG-3 expression in TIL was 6.8 months (95% CI: 5.1-8.6) in the positive group and 6.9 months (95% CI: 2.3-11.5) in the negative group ( p=0.8)]. In multivariate analyses, ECOG performance score, squamous histology, anemia, hypoalbuminemia, high pan immune inflammation value (PIV), low albumin-globulin ratio, radiotherapy to the lung area before nivolumab treatment, presence of metastases in two or more areas other than lymph nodes have been found to be risk factors for OS. Our study could not be demonstrated the contribution of LAG-3 and CD-155 expressions in predicting the results of nivolumab treatment. Although the prognostic importance of various clinical measures has been demonstrated, there is still no biomarker to guide the treatment of NSCLC patients at this stage. Keywords: Non small cell lung cancer, nivolumab, CD-155, LAG-3, biomarker