Abstract 3862: Defining immune contexture in small cell lung cancer: Implications for immunotherapy

Abstract

Abstract Introduction: Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with limited treatment options and median survival approximately 1 year after diagnosis even with treatment. SCLC patients typically respond to platinum-based cytotoxic chemotherapy, but drug resistance and resultant disease progression rapidly develop, driving the 5-year patient survival rate to <5%. The emergence of immunotherapy (IO) offers promising therapeutics for this disease. However, recently FDA approved immunotherapies only improve overall survival (OS) of SCLC patients by 2 months (chemotherapy OS: 10 mos.; chemotherapy + IO OS: 12 mos.). Little is known about the immune landscape in SCLC. We assert that a better understanding of this immune contexture, defined as abundance, type, and location of immune cells, in SCLC may provide important criteria for patient stratification. Objectives: The primary objective of this study is to comprehensively and quantitatively identify immune cell subsets and their associated functional states in small cell lung cancer to address critical knowledge gaps in the tumor biology of the disease. Methods: To broadly/robustly audit immune contexture in SCLC, we generated tissue-microarrays containing >200 unique patient specimens with fully annotated clinical data. Next, we used an innovative and highly multiplex immunohistochemistry (mIHC) platform consisting of a panel of highly validated antibodies and a computational pipeline. Importantly, mIHC enables cell classification via image cytometry, for identification of immune cell subsets, including: T cells (CD3+, CD4, CD8), B cells (CD20+), granulocytes (CD66b+) Th2-skewed monocytes and macrophages (CD11b+ CD68+ CD163+), and dendritic cells (CD68− CD11c+ HLA-DR+, DC-LAMP+/−). Further, functional markers provide insight into immune checkpoints (PD-1, PD-L1), proliferation (Ki67), and T cell functionality (EOMES, granzyme B). Results: Preliminary observations show a wide variability in total immune cell (CD45+) infiltrate, with most infiltrate excluded or peripheral to tumor nests. Further, myeloid immune infiltrates often dominate over lymphoid infiltrates in terms of overall abundance, however variability exists. In particular CD8+ T cells are relatively low in abundance and often excluded from tumor nests in most tumors. Future analysis will deeply phenotype immune cell types and localization, as well as capture interpatient heterogeneity. Conclusions: Understanding the immune landscape of SCLC could further understanding of SCLC immune suppression and evasion, ultimately leading to optimal single-agent immunotherapy deployment and rational, effective combination therapy for patients with SCLC. Citation Format: Portia L. Thomas, Courtney Betts, Giovanney Gonzalez, Lisa M. Coussens, Christine M. Lovly. Defining immune contexture in small cell lung cancer: Implications for immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3862.