Small-cell lung cancer: anatomy of an immune-cold tumor
Millrine, D. Simpson, K. L. Blackhall, F. Dive, C.
Millrine, D.
Simpson, K. L.
Blackhall, F.
Dive, C.
Abstract
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine (NE) tumor and a leading cause of cancer-related morbidity. The introduction of immune checkpoint inhibitors (ICIs) transformed the treatment of many other cancers but has so far failed to benefit all but a minority of SCLC patients who gain a modest increase in overall survival. Although SCLC is often considered to be 'immune-cold', there is no consensus mechanistic view on why most patients fail to respond to ICI therapy. We address this important question by reviewing recent genomic profiling studies that reveal a complex immune landscape. Each molecular subtype is associated with a unique pattern of immune infiltration and a program of cellular plasticity that involves loss of NE traits. This immunobiology presents a rapidly evolving case study in mechanisms of ICI response and resistance. We discuss recent developments, present new hypotheses, and explore future directions for the field.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Millrine D, Simpson KL, Blackhall F, Dive C. Small-cell lung cancer: anatomy of an immune-cold tumor. Trends Cancer. 2025 Dec 8. Epub 2025/12/10.