P72.09 Study of Relationship Between Proportion of CTLA-4 Positive Tregs in Tumor Infiltrating Lymphocytes and PD-L1 TPS

Abstract

KEYNOTE-189 regimen shows a good treatment outcome in patients with previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC) without sensitizing EGFR or ALK mutation. The problem with this regimen is that patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of less than 50% have poorer outcomes than those with a PD-L1 TPS of more than 50%. In 2020, FDA approved CheckMate 9LA regimen as first-line treatment of metastatic or recurrent NSCLC. This regimen is promising because similar therapeutic results were reported regardless of PD-L1 TPS. However, in subgroup analysis, the treatment outcome in the group with a PD-L1 TPS of 50% or more was similar to KEYNOTE-189 regimen. Furthermore, ipilimumab may cause a high frequency of adverse events. Biomarkers are desired for appropriate patient selection. Tumor mutation burden has been attracting attention as a biomarker for predicting the effect of ipilimumab, but it is currently considered negative according to the results of CheckMate 227 study. We focused on cytotoxic T-lymphocyte antigen 4 (CTLA-4) positive regulatory T cells (Tregs), which are considered to be the main therapeutic target of ipilimumab. Tumor tissues resected from 55 patients with NSCLC were homogenized using gentleMACS™ Dissociator (Miltenyi Biotec, Germany), and tumor infiltrating lymphocytes were collected using autoMACS® (Miltenyi Biotec, Germany). Patients with sensitizing EGFR or ALK mutation were excluded. CTLA-4+ CD45RA- forkhead box P3++ Tregs were measured by flow cytometry. Then, we statistically examined the relationship between the proportion of those cells and PD-L1 TPS. The patient background did not vary depending on the PD-L1 TPS. The proportion of CTLA-4+ CD45RA- forkhead box P3++ Tregs in CD8 T cells was constant regardless of PD-L1 TPS (P=0.4857). Lymphocyte counts in peripheral blood did not differ depending on the PD-L1 TPS (P=0.1797). This result suggests that a certain proportion of patients are expected to benefit from CheckMate 9LA regimen, regardless of PD-L1 TPS. Further biomarker study is needed in order to provide appropriate treatment to individual patients.