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Updated: Jun 30, 2026
Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
Peripheral immune cell subsets as potential predictors of benefit from immune checkpoint blockade therapy in small
Miguel A Galindo-Campos1, Max Hardy-Werbin2, Joan Gibert3
1Cancer Research Program, Hospital del Mar Research Institute, Barcelona, Spain.
Background:
Small cell lung cancer (SCLC) is a lethal neoplasia. Chemotherapy (Ct) plus immune checkpoint blockade therapy (ICBt) is now the standard of care although limited survival benefit. Lack of biomarkers of response leads to suboptimal patient selection, distorting results of clinical trials. Deciphering the ICBt-driven peripheral immune events may recognize those patients who benefit the most. Here, we characterize early peripheral immune kinetics in SCLC patients treated with Ct + ICBt with improved survival.
Methods:
SCLC patients from 8 centers were prospectively recruited into 3 cohorts. Cohort 1 (N = 24) include patients treated with Ct. Cohort 2 (N = 37) comprise patients treated with Ct + anti-CTLA-4, and cohort 3 (N = 20) patients treated with Ct + anti-PD-1/PD-L1. Peripheral blood mononuclear cells (PBMCs) were obtained prior to treatment initiation and 3-4 weeks after (before cycle 2). Variation in proliferation, senescence, adhesion, immunosuppression, and checkpoints markers was assessed by Fluorescence-Activated Cell Sorting (FACS). Kaplan-Meier and log-rank test were used for survival analysis. MaxStat was used to calculate cut points. A p-value <0.05 was considered statistically significant.
Results:
We found 6 independent cellular subsets whose modulation shortly after the start of ICBt identify patients with improved survival. An increase in CD8+CD103+Ki67+ cells identify survival benefit in cohorts 1 and 3 (p=0.043; 0.0033). In ICBt cohorts 2 and 3, an upregulation of Ki67 in total CD4+ (p=0.012; 0.0027) and CD4+PD-1+ T cells (p=0.026; 0.027), predicted longer survival, while a downregulation of CD4+ICOS+ T cells (p=0.025; 0.011) identified survival benefit in these same ICBt cohorts. Expansion of Ki67+ and ICOS+ (p=0.0024; 0.0074) CD8+ T cells was also observed in CD8+ T cells from long survivors exclusively from cohort 2.
Conclusions:
This study provides one of the few longitudinal assessments of peripheral immune dynamics in SCLC patients receiving ICBt, suggesting that early on-treatment changes, evaluated relative to each patient's own baseline levels, may provide greater predictive value than single-timepoint inter-patient comparisons.
Insights
Early changes in peripheral immune cells can predict survival in small cell lung cancer (SCLC) patients treated with chemotherapy plus immune checkpoint blockade therapy (ICBt). Monitoring these immune dynamics offers a potential biomarker for treatment response.
Area of Science:
- Immunology
- Oncology
- Translational Research
Background:
- Small cell lung cancer (SCLC) has a poor prognosis despite current standard of care (chemotherapy + immune checkpoint blockade therapy - ICBt).
- Limited survival benefits from ICBt are partly due to a lack of predictive biomarkers for patient selection.
- Understanding peripheral immune responses to ICBt may identify patients who benefit most.
Purpose of the Study:
- To characterize early peripheral immune kinetics in SCLC patients receiving chemotherapy plus ICBt.
- To identify immune cell subsets and their dynamic changes that correlate with improved survival.
Main Methods:
- Prospective study of SCLC patients across three cohorts: chemotherapy alone, chemotherapy + anti-CTLA-4, and chemotherapy + anti-PD-1/PD-L1.
- Peripheral blood mononuclear cells (PBMCs) analyzed pre-treatment and after the first cycle using Fluorescence-Activated Cell Sorting (FACS).
- Assessed variations in cell proliferation, senescence, adhesion, immunosuppression, and checkpoint markers; survival analyzed using Kaplan-Meier and log-rank tests.
Main Results:
- Six independent cellular subsets modulated early after ICBt initiation predicted improved survival.
- Increased CD8+CD103+Ki67+ cells correlated with survival benefit in chemotherapy and chemotherapy + anti-PD-1/PD-L1 cohorts.
- Upregulation of Ki67 in CD4+ and CD4+PD-1+ T cells, and downregulation of CD4+ICOS+ T cells, predicted longer survival in ICBt cohorts.
- Expansion of Ki67+ and ICOS+ CD8+ T cells was observed in long-term survivors of the chemotherapy + anti-CTLA-4 cohort.
Conclusions:
- Early on-treatment peripheral immune dynamics in SCLC patients receiving ICBt can predict survival outcomes.
- Longitudinal assessment of immune changes relative to baseline offers greater predictive value than single time-point comparisons.
- These findings suggest potential biomarkers for identifying SCLC patients likely to benefit from ICBt.
