IgM-Rheumatoid factor confers primary resistance to anti-PD-1 immunotherapies in NSCLC patients by reducing CD137
Aged
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Disease Progression
Drug Resistance, Neoplasm
Female
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Immunoglobulin M
/ blood
Lung Neoplasms
/ drug therapy
Lymphocyte Activation
/ genetics
Male
Middle Aged
Molecular Targeted Therapy
Prognosis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Retrospective Studies
Rheumatoid Factor
/ blood
T-Lymphocytes
/ drug effects
Tumor Necrosis Factor Receptor Superfamily, Member 9
/ metabolism
CD137(+) T-cells
IgM-rheumatoid factor
NSCLC
Prognostic biomarker
Survival
anti-PD-1 ICIs
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
19
06
2020
revised:
07
09
2020
accepted:
14
10
2020
pubmed:
10
11
2020
medline:
25
8
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137 Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated. IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naïve and central memory T-cells and a significant reduction of CD137 In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naïve and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137 AIRC, MIUR and Sapienza University of Rome.
Sections du résumé
BACKGROUND
BACKGROUND
ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137
METHODS
METHODS
Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated.
FINDINGS
RESULTS
IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naïve and central memory T-cells and a significant reduction of CD137
INTERPRETATION
CONCLUSIONS
In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naïve and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137
FUNDINGS
RESULTS
AIRC, MIUR and Sapienza University of Rome.
Identifiants
pubmed: 33166793
pii: S2352-3964(20)30474-6
doi: 10.1016/j.ebiom.2020.103098
pmc: PMC7658668
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Immunoglobulin M
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
TNFRSF9 protein, human
0
Tumor Necrosis Factor Receptor Superfamily, Member 9
0
Rheumatoid Factor
9009-79-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103098Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors declare no competing interests.