Longitudinal blood immune-inflammatory and radiomic profiling to decode different patterns of acquired resistance to immunotherapy in patients with NSCLC.

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2024-12-13 DOI:10.1158/1078-0432.CCR-24-1926

Giulia Mazzaschi, Cristina Marrocchio, Lucas Moron Dalla Tor, Ludovica Leo, Maurizio Balbi, Gianluca Milanese, Ganiyat A R Adebanjo, Bruno Lorusso, Gregorio Monica, Monica Pluchino, Roberta Minari, Simona D'Agnelli, Elisa Cardinale, Fabiana Perrone, Paola Bordi, Alessandro Leonetti, Roberta E Ledda, Mario Silva, Sebastiano Buti, Giovanni Roti, Stefano Bettati, Federico Quaini, Marcello Tiseo, Nicola Sverzellati

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引用次数: 0

Abstract

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors.

Experimental design: On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3). Clinico-pathological, PB and radiomic parameters and survival outcome were statistically correlated to AR patterns.

Results: OligoAR and sysAR involved 24% and 12.4% of cases, respectively. While baseline PB immune profiles were comparable, a Δpos cytotoxic (NK, CD8+GnzB+) and Δneg immunosuppressive (CD14+ monocytes) dynamic coupled with different modulation of IL-6, TGF-β1, TNFα and sPD-L1 represented distinctive features of oligoAR vs sysAR (P<0.05). Significantly longer post-progression survival characterized oligoAR vs sysAR (median 20.3 vs 5.6 months;HR:0.22,P<0.001). The number and sites of oligoAR involvement appeared to condition blood immune background (P<0.05) and survival. Delta radiomic outperformed baseline RFs, with 15 ΔRFs sharply discriminating oligoAR from sysAR (P range:<0.001-0.04). ROC analysis confirmed the optimal performance of top-ranked ΔRFs (AUC range:0.88-0.99).

Conclusions: Longitudinal analysis of blood immune hallmarks and radiomic descriptors may decipher distinct patterns of AR to IO in advanced NSCLC patients.

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.