Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Jair Bar ^1,2, Raya Leibowitz ^2,3, Niels Reinmuth ^4,5

¹Institute of Oncology, Chaim Sheba Medical Center, Tel Hashomer, Israel.
²Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
³Shamir Medical Center, Oncology Institute, Zerifin, Israel.
⁴German Center for Lung Research (DZL), Munich-Gauting, Germany.
⁵Biobank of lung disease, Asklepios Klinik Gauting GmbH, Gauting, Germany.
⁶OncoHost LTD, Binyamina, Israel.
⁷Thoracic oncology service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
⁸Biobank, Department of Pathology, Rabin Medical Center, Petah Tikva, Israel.
⁹Center for Melanoma and Cancer Immunotherapy, Hadassah Hebrew University Medical Center, Sharett Institute of Oncology, Jerusalem, Israel.
¹⁰Department of Oncology, Kaplan Medical Center, Rehovot, Israel.
¹¹Institute of Oncology, Bnai Zion Medical Center, Haifa, Israel.
¹²Oncology & Hematology Division, Cancer Center, Emek Medical Center, Afula, Israel.
¹³Department of Oncology, Meir Medical Center, Kfar-Saba, Israel.
¹⁴Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Ashkelon, Israel.
¹⁵Division of Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹⁶Department of Oncology, Assuta Hospital, Tel Aviv, Israel.
¹⁷Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States.
¹⁸Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

⁰Institute of Oncology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Frontiers in Immunology +

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March 15, 2024

View abstract on PubMed

Summary

Early on-treatment plasma proteomics reveal biomarkers for non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI). Soluble PD-1 and T cell activation markers correlate with treatment response, while alveolar proteins may indicate limited benefit.

Area Of Science

Oncology
Immunology
Proteomics

Background

Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment.
Predictive biomarkers for patient stratification in ICI therapy are currently lacking.
Understanding early on-treatment proteomic changes is crucial for deciphering response and resistance.

Purpose Of The Study

To characterize early proteomic alterations in plasma during ICI-based therapy for NSCLC.
To identify novel plasma protein biomarkers associated with clinical benefit and overall survival.
To explore the biological processes and cellular origins of proteomic changes during treatment.

Main Methods

Collected pre-treatment (T0) and on-treatment (T1) plasma samples from 225 NSCLC patients undergoing ICI regimens.
Utilized aptamer-based technology to quantify approximately 7000 plasma proteins per sample.
Analyzed significant protein fold changes (T1:T0) and correlated them with clinical outcomes (clinical benefit, overall survival).

Main Results

142 proteins showed significant upregulation post-ICI treatment, including soluble PD-1, which correlated with tumor PD-L1 status and improved survival in monotherapy.
A 30-protein network, including CD8A, indicated T cell activation during ICI treatment, irrespective of clinical benefit.
Upregulated proteins of alveolar origin were associated with limited clinical benefit, potentially linked to cellular stress and lung damage.

Conclusions

Plasma proteomics can reveal biological processes activated during ICI therapy.
Identified soluble PD-1 and T cell activation markers as potential prognostic indicators.
Circulating alveolar proteins may serve as biomarkers for predicting limited response to ICI therapy in NSCLC.

Keywords:

NSCLC PD-1 PD-L1 biological process proteomics

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Tumor Immunotherapy

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