MA09.05 PD1-Positive Tertiary Lymphoid Structure as a Predictive Factor of Durable Clinical Effect in Immunotherapy for NSCLC

There is urgent need for accurate biomarkers in immunotherapy (IO) for advanced or recurrent lung cancer. In 2020, tertiary lymphoid structure (TLS) of cancer tissue was reported to be related with IO response and is attracting attention as a new biomarker. In the current study, we investigated whether TLS and its lymphocyte distribution are associated with durable clinical effect (DCR) by IO in postoperative recurrent non-small cell lung cancer (NSCLC) patients. Between 2016 and 2019, 55 patients were treated with IO for recurrent NSCLCs. Tumor pathology and TLS were evaluated by H&E and immunohistochemical staining. DCR was defined as ‘tumor maintaining stable disease or better for more than one year after IO’, and the patients were divided to DCR and non-DCR group. Their clinicopathological factors, the number of TLS or tumor infiltrating lymphocytes (TIL) and lymphocytic subset in TLS were compared between the two groups. The median age of all 55 patients was 68 years and 43 (78%) of them were men. Histological types of their tumors were 39 (71%) adenocarcinomas, 8 (15%) squamous cell carcinomas, and 3 (6%) large cell neuroendocrine carcinomas. DCR was observed in 14 (26%) patients, and included significantly younger patients (70 years old or less), more PD-L1 expression scores (TPS), more CD8-positive TIL, more PD1-positive TLS (PD1+TLS) and more immune-related adverse event (irAE, Grade 3 and more) than non-DCR group. There were not significant differences in pathological findings including histological type, pathological stage, pleural invasion, vessel invasion, predominant subtypes in adenocarcinoma. Multivariate analysis revealed that age, PD1+TLS and irAE were independent predictive factors of DCR. In DCR group, 1- and 3-year overall survival (OS) rate after IO treatment was 100 and 81%, respectively, while those in non-DCR group were 37 and 7%, respectively. Their post-IO OS curves were significantly different (p <0.01). We explored predictive factors for DCR in IO-treated recurrent NSCLC patients. PD1+ TLS was an independent positive factor of DCR.