Facts and hopes on cancer immunotherapy for small cell lung cancer

Clin Cancer Res. 2024 Apr 17. doi: 10.1158/1078-0432.CCR-23-1159. Online ahead of print.ABSTRACTPlatinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including, among others, T cell exclusion, downregulation of components of the MHC-class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints. New immunotherapies aiming to target some of these dominant immune suppressive features are being intensively evaluated preclinically and clinically in SCLC. They include strategies to enhance the efficacy and/or reverse features that promote intrinsic resistance to PD-1 axis inhibition (e.g., restoring MHC-class I deficiency, targeting DNA damage response [DDR]), and novel immunomodulatory agents beyond T cell checkpoint blockers (e.g., T cell redirecting strategies, antibody drug conjugates [ADCs], or macrophage checkpoint blockers). Among them, DLL3-targeted bi-specific T-cell engagers (BiTEs) are the ones that have shown the most compelling preliminary evidence of clinical efficacy, and hold promise as therapies that might contribute to further improve patient ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Source Type: research