Abstract 7160: The distribution of tertiary lymphoid structures serves as a hallmark of hot tumors and is associated with long-term survival and the efficacy of immune checkpoint inhibitors in patients with small cell lung cancer: A retrospective and

Abstract Tertiary lymphoid structures (TLSs) are ectopic lymphoid organs capable of predicting the outcome and therapeutic response in various tumors. Nevertheless, the distribution and clinical significance of TLSs in small cell lung cancer (SCLC) have never been explored. Here, we enrolled over 1500 cases from 6 centers in this retrospective and prospective analysis to elucidate the immune landscape and predictive value of TLSs in SCLC. By employing immunohistochemistry (CD3, CD20, CD21, and CD23) and RNA-seq analysis, we discovered that a high abundance of TLSs was associated with a lower recurrence rate and long-term survival in patients with resected SCLCs. Univariate and multivariate analyses indicated that the status of TLSs was significantly correlated with a lower risk of relapse and cancer-specific death (P<0.01), independent of clinicopathological and molecular classifications (ASCL1, NEUROD1, POU2F3, and YAP1). Through the analysis of single-cell RNA sequencing data from 6 patients and whole slide digital pathology analysis of immunohistochemistry (CD45RO, CD4, CD8, CD14, CD68, CD163, CD57, CD66b, Foxp3, and PD-L1) from more than 600 patients, we found that tumors with a high abundance of TLSs were characterized by a high proportion of effector T cells and a high infiltration of anti-tumor immune cells. More importantly, we demonstrated that the status of TLSs was associated with an improved objective response rate, progression-free survival, and overall survival independently of CD8+ T-cell density in SCLCs with immune checkpoint inhibitors from 2 independent retrospective cohorts and a prospective cohort. In summary, our findings highlight that TLSs is a hallmark of hot tumors in SCLC and represents a promising biomarker for long-term survival and immunotherapy. Citation Format: Chaoqi Zhang, Peng Wu, Le Wang, Dexin Shang, Junhan Zhou, Jingjing Liu, Chunqi Lin, Nan Sun, Jie He. The distribution of tertiary lymphoid structures serves as a hallmark of hot tumors and is associated with long-term survival and the efficacy of immune checkpoint inhibitors in patients with small cell lung cancer: A retrospective and prospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7160.