Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers

Journal of Hematology & Oncology, 2024 · DOI: https://doi.org/10.1186/s13045-024-01534-9 · Published: March 11, 2024

Simple Explanation

Immunotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC), but many patients don't respond due to resistance and a lack of good predictive markers. This study used proteomic analysis to explore why some ESCC patients respond to anti-PD1 immunotherapy while others don't. The study found that immune and mitochondrial functions are linked to immunotherapy sensitivity, while platelet activation is negatively correlated with CD8+ T cells and is associated with non-sensitivity. This suggests platelets may interfere with the effectiveness of CD8+ T cells. Researchers identified 10 potential biomarkers that accurately predict ESCC immunotherapy response. These biomarkers were validated in an independent group of patients, showing their potential for identifying patients who will benefit from immunotherapy.

Study Duration

Not specified

Participants

73 ESCC patients

Evidence Level

Not specified

Key Findings

1
Immune and mitochondrial functions are associated with ESCC immunotherapy sensitivity.
2
Platelet activation shows a negative correlation with CD8+ T cells and is related to ESCC immunotherapy non-sensitivity, suggesting platelets may impair CD8+ T cell function.
3
Ten potential ESCC immunotherapy predictive biomarkers were identified with high accuracy (≥ 0.90) and validated in an independent cohort.

Research Summary

This study investigates the proteomic landscape of esophageal squamous cell carcinoma (ESCC) in response to anti-PD1 immunotherapy to identify resistance mechanisms and predictive markers. The research reveals that immune and mitochondrial functions are linked to immunotherapy sensitivity, while platelet activation is associated with non-sensitivity by potentially impairing CD8+ T cell function. The study identifies and validates ten predictive biomarkers for ESCC immunotherapy response, offering a means to distinguish sensitive from non-sensitive patients.

Practical Implications

Predictive Biomarkers for Immunotherapy Response

The identified biomarkers could help personalize immunotherapy treatment for ESCC patients by identifying those most likely to respond.

Therapeutic Strategies Targeting Platelet Activation

The finding that platelet activation is associated with immunotherapy resistance suggests that targeting platelet activation could enhance immunotherapy efficacy.

Understanding Resistance Mechanisms

The study provides insights into the mechanisms of immunotherapy resistance in ESCC, which can inform the development of new therapeutic strategies.

Study Limitations

1
The study acknowledges the object response rate (ORR) was only 54.2% for ESCC immunotherapy.
2
The study mentions challenges in screening patients suitable for immunotherapy due to the limitation in the specificity and sensitivity of existing companion diagnostic markers.
3
Further research may be needed to fully elucidate the direct physical interaction between platelets and CD8+ T cells.

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