Dataset Information

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

ABSTRACT:

Introduction

While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.

Methods

Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.

Results

Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort.

Discussion

Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

SUBMITTER: Szadai L

PROVIDER: S-EPMC11249723 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

Szadai Leticia L Bartha Aron A Parada Indira Pla IP Lakatos Alexandra I T AIT Pál Dorottya M P DMP Lengyel Anna Sára AS de Almeida Natália Pinto NP Jánosi Ágnes Judit ÁJ Nogueira Fábio F Szeitz Beata B Doma Viktória V Woldmar Nicole N Guedes Jéssica J Ujfaludi Zsuzsanna Z Pahi Zoltán Gábor ZG Pankotai Tibor T Kim Yonghyo Y Győrffy Balázs B Baldetorp Bo B Welinder Charlotte C Szasz A Marcell AM Betancourt Lazaro L Gil Jeovanis J Appelqvist Roger R Kwon Ho Jeong HJ Kárpáti Sarolta S Kuras Magdalena M Murillo Jimmy Rodriguez JR Németh István Balázs IB Malm Johan J Fenyö David D Pawłowski Krzysztof K Horvatovich Peter P Wieslander Elisabet E Kemény Lajos V LV Domont Gilberto G Marko-Varga György G Sanchez Aniel A

Frontiers in oncology 20240702

<h4>Introduction</h4>While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.<h4>Methods</h4>Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.<h4>Results</h4>Si ...[more]

PMID: 39015503

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Project description:PurposeImmune checkpoint inhibitors can induce a T cell-mediated anti-tumor immune response in patients with melanoma. Visualizing T cell activity using positron emission tomography (PET) might allow early insight into treatment efficacy. Activated tumor-infiltrating T cells express the high-affinity interleukin-2 receptor (IL-2R). Therefore, we performed a pilot study, using fluorine-18-labeled IL-2 ([18F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected.MethodsPatients with metastatic melanoma received ~ 200 MBq [18F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [18F]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUVmean) and tumor lesions (SUVmax). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration.ResultsBaseline [18F]FB-IL2 PET scans were performed in 13 patients. SUVmean at baseline was highest in the kidneys (14.2, IQR: 11.6-18.0) and liver (10.6, IQR: 8.6-13.4). In lymphoid tissues, uptake was highest in spleen (10.9, IQR: 8.8-12.4) and bone marrow (2.5, IQR: 2.1-3.0). SUVmax in tumor lesions (n = 41) at baseline was 1.9 (IQR: 1.7-2.3). In 11 patients, serial imaging was performed, three at week 6, seven at week 2, and one at week 4. Median [18F]FB-IL2 tumor uptake decreased from 1.8 (IQR: 1.7-2.1) at baseline to 1.7 (IQR: 1.4-2.1) during treatment (p = 0.043). Changes in [18F]FB-IL2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [18F]FB-IL2 uptake. No [18F]FB-IL2-related side effects occurred.ConclusionPET imaging of the IL-2R, using [18F]FB-IL2, is safe and feasible. In this small patient group, serial [18F]FB-IL2-PET imaging did not detect a treatment-related immune response.Trial registrationClinicaltrials.gov : NCT02922283; EudraCT: 2014-003387.20.

Dataset Information

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

Introduction

Methods

Results

Discussion

Publications

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

Similar Datasets

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