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Open Access 05-09-2023 | SCLC | Research

Leptin-mediated meta-inflammation may provide survival benefit in patients receiving maintenance immunotherapy for extensive-stage small cell lung cancer (ES-SCLC)

Authors: Emanuele Vita, Alessio Stefani, Geny Piro, Luca Mastrantoni, Marco Cintoni, Giuseppe Cicchetti, Ileana Sparagna, Federico Monaca, Guido Horn, Jacopo Russo, Diletta Barone, Mariantonietta Di Salvatore, Rocco Trisolini, Filippo Lococo, Ciro Mazzarella, Alessandra Cancellieri, Carmine Carbone, Anna Rita Larici, Maria Cristina Mele, Sara Pilotto, Michele Milella, Giampaolo Tortora, Emilio Bria

Published in: Cancer Immunology, Immunotherapy | Issue 11/2023

Abstract

Background

Only few ES-SCLC patients experience long-term survival benefit by maintenance IT. Adipokines-induced metabolic meta-inflammation has been related to enhanced responsiveness to IT in obese patients; however, their prognostic role in SCLC is currently controversial.

Methods

Pre-treatment CT scan was used for determining distribution of abdominal adiposity, and blood samples were collected at fasting for measuring glycemia, insulin, ghrelin, leptin and adipokines (TNF-α, IFN-γ, IL-6 and MCP-1). Patients with known history of DM type II or metabolic syndrome with HOMA index > 2.5 were considered insulin resistant (IR).

Results

In ES-SCLC pts receiving maintenance IT, increased leptin concentration and higher leptin/visceral adipose tissue (VAT) ratio were significantly associated with prolonged PFS. By applying a hierarchical clustering algorithm, we identified a cluster of patients characterized by higher leptin values and lower pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) who experienced longer PFS (13.2 vs 8.05 months; HR: 0.42 [0.18–0.93] p = 0.02) and OS (18.04 vs 12.09 mo; HR: 0.53 [0.25–1.29] p = 0.07).

Conclusions

Adipokines can play a crucial role to determining effectiveness of anti-cancer immunotherapy. The role of metabolic immune dysfunctions needs further pre-clinical validation and is currently investigated in the larger prospective cohort.

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Title: Leptin-mediated meta-inflammation may provide survival benefit in patients receiving maintenance immunotherapy for extensive-stage small cell lung cancer (ES-SCLC)
Authors: Emanuele Vita
Alessio Stefani
Geny Piro
Luca Mastrantoni
Marco Cintoni
Giuseppe Cicchetti
Ileana Sparagna
Federico Monaca
Guido Horn
Jacopo Russo
Diletta Barone
Mariantonietta Di Salvatore
Rocco Trisolini
Filippo Lococo
Ciro Mazzarella
Alessandra Cancellieri
Carmine Carbone
Anna Rita Larici
Maria Cristina Mele
Sara Pilotto
Michele Milella
Giampaolo Tortora
Emilio Bria
Publication date: 05-09-2023
Publisher: Springer Berlin Heidelberg
Keywords: SCLC
SCLC
Obesity
Obesity
Insulins
Insulins
Cytokines
Published in: Cancer Immunology, Immunotherapy / Issue 11/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03533-0

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Abstract

Background

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