Exploring YAP1-related TIME in SCLC: implications for survival and treatment response to immuno-chemotherapy

Aim: Small-cell lung cancer (SCLC) is usually diagnosed as an advanced stage with a poor outcome. SCLC has limited response to immunotherapy due to the absence or lack of immune cell infiltration, so studying its tumor immune microenvironment (TIME) is essential. Methods: The study involved patients with extensive-stage small-cell lung cancer (ES-SCLC) diagnosed at the Guangdong Lung Cancer Institute between January 2018 and April 2022 who had received the atezolizumab/carboplatin/etoposide (ECT) treatment. We used multi-immunohistochemistry (mIHC) to assess the prognostic value of YAP1 and TIME in SCLC, with results confirmed using public data. Results: 15 patients with sufficient baseline biopsy samples were included in this study. The total population of YAP1-positive cells is inversely related to progression-free survival (PFS) and shows a potential negative correlation with overall survival (OS). CD56-positive cells are the primary components of TIME in SCLC tumor parenchyma and stroma. The total population and cell density of YAP1-positive cells are significantly positively correlated with CD4-positive cells. Furthermore, in the tumor parenchyma, both the proportion and the cell density of YAP1-positive cells are positively correlated with that of FOXP3-positive cells. The total population of CD56-positive cells showed a negative correlation trend with YAP1-positive cells but without significant difference. Conclusion: YAP1 has shown prognostic value in SCLC patients receiving ECT regimen treatment. The high expression level of YAP1 seems related to the inhibitory TIME. However, some prospective studies with larger populations are warranted.