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Published on: October 11, 2018
Plasma proteomics identifies leukemia inhibitory factor (LIF) as a novel predictive biomarker of immune-checkpoint
Y Loriot1, A Marabelle2, J P Guégan3
1Cancer Medicine Department, INSERM U981, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Background:
Immune checkpoint blockers (ICBs) are now widely used in oncology. Most patients, however, do not derive benefit from these agents. Therefore, there is a crucial need to identify novel and reliable biomarkers of resistance to such treatments in order to prescribe potentially toxic and costly treatments only to patients with expected therapeutic benefits. In the wake of genomics, the study of proteins is now emerging as the new frontier for understanding real-time human biology.
Patients And Methods:
We analyzed the proteome of plasma samples, collected before treatment onset, from two independent prospective cohorts of cancer patients treated with ICB (discovery cohort n = 95, validation cohort n = 292). We then investigated the correlation between protein plasma levels, clinical benefit rate, progression-free survival and overall survival by Cox proportional hazards models.
Results:
By using an unbiased proteomics approach, we show that, in both discovery and validation cohorts, elevated baseline serum level of leukemia inhibitory factor (LIF) is associated with a poor clinical outcome in cancer patients treated with ICB, independently of other prognostic factors. We also demonstrated that the circulating level of LIF is inversely correlated with the presence of tertiary lymphoid structures in the tumor microenvironment.
Conclusion:
This novel clinical dataset brings strong evidence for the role of LIF as a potential suppressor of antitumor immunity and suggests that targeting LIF or its pathway may represent a promising approach to improve efficacy of cancer immunotherapy in combination with ICB.
Insights
Elevated leukemia inhibitory factor (LIF) in blood predicts poor response to immune checkpoint blockers (ICBs) in cancer patients. Targeting LIF may improve immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Proteomics
Background:
- Immune checkpoint blockers (ICBs) are a key cancer therapy, but many patients lack benefit.
- Identifying biomarkers for ICB resistance is crucial for optimizing treatment.
- Proteomics offers a window into real-time human biology for biomarker discovery.
Purpose of the Study:
- To identify reliable protein biomarkers predicting response to ICB therapy.
- To investigate the role of specific proteins in mediating resistance or sensitivity to ICBs.
Main Methods:
- Proteomic analysis of plasma samples from two independent cohorts of cancer patients (n=95 and n=292) before ICB treatment.
- Correlation analysis of protein levels with clinical benefit, progression-free survival, and overall survival using Cox proportional hazards models.
Main Results:
- Elevated baseline serum levels of leukemia inhibitory factor (LIF) were associated with poor clinical outcomes in both cohorts.
- LIF levels were independent of other prognostic factors and inversely correlated with tertiary lymphoid structures in the tumor microenvironment.
Conclusions:
- Leukemia inhibitory factor (LIF) shows potential as a biomarker for ICB resistance.
- LIF may suppress antitumor immunity, suggesting it as a therapeutic target to enhance cancer immunotherapy efficacy.
