WCLC Sept 2021 | Exploring the factors facilitating metastasis in SCLC

Joseph M Chan, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, describes the results from a study aiming to explain the high metastatic potential of small cell lung cancer (SCLC) through characterization of tumor diversity and of the tumor immune microenvironment with single-cell RNA sequencing (scRNA-seq), and proteomic spatial imaging. To begin with, it was found that SCLC has a higher tumor diversity than other lung cancer subtypes. Tumor diversity was mainly driven by canonical transcriptional subtypes, of which the most common are SCLC-A and SCLC-N. The SCLC-N subtype was found at increased frequencies at metastatic sites where it was shown to promote axonogenesis, which is known to promote metastasis in SCLC. Moreover, the study reported that PLCG2-high cancer populations were present in a large number of patients regardless of their predominant SCLC subtype. PLCG2 is known to mediate cell motility and experiments demonstrated that PLCG2 overexpression increased metastasis in SCLC and was correlated with worse overall survival (OS). Analysis of the immune microenvironment showed that immune cells were sequestered from the bulk of the tumor and that there was an increase in T regulatory cells (Tregs) and a decrease in cytotoxic cells, with an overall decreased abundance of immune cells in the SCLC-N subtype. In addition, pro-fibrotic myeloid cells present at the site of the tumor correlated with the presence of PLCG2-high recurrent tumor cell populations, suggesting that these myeloid cells could be facilitating metastasis. The data from this study is available online on the Human Tumor Atlas Network (HTAN). This interview took place at the World Conference on Lung Cancer (WCLC) 2021.