Abstract 6152: Distinct immune gene programs associated with host tumor immunity, neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC

Abstract Background: Our understanding of the immunopathology of early-stage NSCLC is still limited. While neoadjuvant immunotherapeutic strategies have recently shown anti-tumor effects in resectable NSCLC, their mechanisms remain inadequately understood. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC. Methods: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n=190), neoadjuvant chemotherapy (n=38) and neoadjuvant chemoimmunotherapy (n=21). Three tumor immune microenvironment (TIME) phenotypes (inflamed, cold, excluded) were derived based on CD8+ T cell infiltration. Signatures of immune cell abundance and immune genes were statistically compared based on tumoral PD-L1 expression, immune phenotypes, associated with pathological response, and were cross-compared across the three cohorts. Results: PD-L1 positive tumors exhibited increased signature scores for various lymphoid and myeloid cell subsets (both, p<0.05). TIME phenotypes exhibited disparate frequencies by stage, PD-L1 expression, and mutational burden. Inflamed NSCLCs displayed overall significantly heightened levels of immune signatures with the excluded group representing an intermediate state. A signature of cytotoxic T cells was associated with favorable survival in neoadjuvant chemotherapy-treated NSCLCs (p<0.05). Major pathological response to chemoimmunotherapy was positively associated with CD8 T cells (p<0.05) and Th1 cells were significantly reduced post-chemoimmunotherapy (p<0.001). Among the three cohorts, chemoimmunotherapy-treated NSCLCs exhibited highest scores for various immune cell subsets including T effector and B cells (both, p<0.05). Conclusions: Our findings highlight immune gene programs that may underlie host tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in early-stage NSCLC. Citation Format: Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Katsuhiro Yoshimura, Carmen Behrens, Apar Pataer, Edwin Parra-Cuentas, Cara Haymaker, Junya Fujimoto, Stephen Swisher, John Heymach, Don L. Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M. Solis, Mariano Provencio, Ignacio I. Wistuba, Humam Kadara. Distinct immune gene programs associated with host tumor immunity, neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6152.