Predictive biomarkers for immunotherapy response in extensive-stage SCLC

Sep 22, 2026

Upload by Logic

Small cell lung cancer (SCLC) comprises about 13–15% of lung cancers, and most patients present with extensive-stage disease (ES-SCLC). While immunotherapy combined with chemotherapy is now a standard first-line approach, ES-SCLC remains largely “immune-cold,” with limited beneficiaries and brief response duration. Biomarkers are needed to identify patients likely to benefit from immunotherapy, yet clinically applicable predictive biomarkers in SCLC are not well established.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Purpose

Conclusion

Introduction

Epidemiology and treatment background

Role of immune checkpoint inhibitors

Predictive biomarker landscape

Journal of Cancer Research and Clinical Oncology (2024) 150:22 [https://doi.org/10.1007/s00432-023-05544-x](https://doi.org/10.1007/s00432-023-05544-x) Predictive biomarkers for immunotherapy response in extensive‑stage SCLC Lin Zhu1 · Jing Qin1,2 Received: 9 October 2023 / Accepted: 13 December 2023 / Published online: 20 January 2024 © The Author(s) 2024 Abstract Background Small cell lung cancer (SCLC) accounts for about 13–15% of all lung cancers, and about 70% of SCLC patients have developed extensive-stage small cell lung cancer (ES-SCLC) at the time of diagnosis because of its highgrade malignancy, easy invasion, and metastasis. In recent years, immunotherapy combined with chemotherapy has become the standard first-line treatment for ES-SCLC. However, SCLC is a relatively immune-cold lung cancer subtype with a limited number of beneficiaries and a short benefit period. Therefore, the use of biomarkers to identify populations with significant benefits from immunotherapy will help improve the efficacy and survival benefits of immunotherapy. However, predictive biomarkers suitable for clinical practice have not been established in the field of SCLC. Purpose In order to find the predictive biomarkers of immunotherapy for ES-SCLC, we summarized the research progress of traditional biomarkers, such as programmed cell death ligand 1 (PD-L1) and tumor mutation burden (TMB), and summarizes the research of potential biomarkers associated with prognosis, such as molecular subtypes, special gene expression, expression of major histocompatibility complex (MHC) I and II classes, tumor immune microenvironment (TIME), and circulating tumor DNA (ctDNA) .We aim to provide new insights on biomarkers. Conclusion The exploration of biomarkers for immunotherapy of SCLC is still very difficult, and it is clear that conventional predictive biomarkers are not suitable for SCLC. At present, the molecular subtypes defined from transcription factors may have some guiding significance, which still needs to be confirmed by prospective clinical studies. In addition, the ctDNA positivity rate of SCLC is higher than that of other tumor types, which can also solve the dilemma of the difficulty of obtaining specimens of SCLC tissues. And the dynamic change of ctDNA also has great potential to predict the curative effect of SCLC, which is worth further clinical exploration. Keywords SCLC · Immunotherapy · Biomarkers · Molecular subtypes · ctDNA Introduction Among new cancer cases, lung cancer is the second most prevalent (11.4%) and the first most mortality (18%) worldwide, according to GLOBOCAN (Sung et al. 2021) . According to the pathological types, lung cancer is divided into two * Jing Qin [qinjing@zjcc.org.cn](qinjing@zjcc.org.cn) 1 Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China 2 Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou 310022, People’s Republic of China subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Among them, SCLC accounts for about 13–15% of all lung cancers. Due to its high degree of malignancy and easy of invasion and metastasis, about 70% of SCLC patients have developed extensive small-cell lung cancer (ES-SCLC) at the time of diagnosis. In previous studies, ES-SCLC was highly sensitive to platinum chemotherapy (carboplatin or cisplatin) with etoposide in standard first-line treatment, with response rates of 60%–65%(Hornet al. 2018). Despite the high response rate, the prognosis of ES-SCLC patients was poor, with a median overall survival (mOS) of 9–11 months, a 1-year overall survival (OS) rate of 35%, a 2-year OS rate not exceeding 5%, and a 5-year OS rate of only 3%(Rudin et al. 2021 ; Farago and Keane 2018; Byers and Rudin 2015) . SCLC has a high mutation rat

FAQs

Why are predictive biomarkers needed for extensive-stage SCLC immunotherapy?

Because ES-SCLC is relatively immune-cold and only a limited number of patients benefit for a short period, biomarkers are needed to identify those who gain significant benefit and improve efficacy and survival outcomes.

Which conventional biomarkers are discussed as candidates for predicting immunotherapy response?

The document highlights traditional biomarkers such as PD-L1 and tumor mutation burden (TMB) as examples of currently studied predictive biomarkers.

What potential biomarkers does the paper consider beyond conventional markers?

It summarizes potential biomarkers linked to prognosis, including molecular subtypes, special gene expression, MHC I/II expression, tumor immune microenvironment (TIME), and circulating tumor DNA (ctDNA).

What does the conclusion say about the usefulness of current predictive biomarkers and ctDNA?

It states that conventional predictive biomarkers are not suitable for SCLC, while transcription-factor-defined molecular subtypes may offer guiding significance that needs prospective confirmation. It also notes that ctDNA positivity is higher and that dynamic ctDNA changes may predict therapeutic effect and warrant further clinical exploration.

Sep 22, 2026

Upload by Logic