Biomarker-Driven Insights into Immune Checkpoint Inhibitor Therapy in Small-Cell Lung Cancer
Shuxing Wang1, Xinrui Zhao1, Yue Zeng2
1Departmen(t) of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China; Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
Critical Reviews in Oncology/Hematology
|August 6, 2026
Summary
Biomarkers are crucial for understanding small cell lung cancer (SCLC) treatment resistance to immune checkpoint inhibitors (ICIs). Identifying these biomarkers can help overcome resistance and improve patient outcomes.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Small cell lung cancer (SCLC) is an aggressive cancer with limited treatment options.
- Immune checkpoint inhibitors (ICIs) have improved SCLC treatment, but resistance and lack of predictive biomarkers are significant challenges.
Purpose of the Study:
- To review the role of biomarkers in SCLC treatment resistance.
- To explore tumor-intrinsic, tumor microenvironment (TME), and systemic host factors influencing ICI efficacy.
Main Methods:
- Literature review focusing on biomarkers in SCLC and their association with ICI response.
- Analysis of tumor-intrinsic features (molecular subtypes, mutations), TME components (PD-L1, TILs), and systemic factors (ctDNA, CTCs, host immunity).
Main Results:
- Tumor-intrinsic features like the SCLC-I subtype and TMB show varying associations with ICI efficacy.
- TME factors such as CD8+ TILs, regulatory T cells, and PD-L1 expression modulate anti-tumor response.
- Systemic factors, including circulating tumor DNA (ctDNA) and host immune cell phenotypes, offer insights into treatment response.
Conclusions:
- Biomarkers are pivotal in understanding and overcoming SCLC treatment resistance.
- Further validation of biomarkers and investigation of combination therapies are needed to improve patient outcomes.
