Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients.
Humans
Melanoma
/ drug therapy
Male
Receptors, Immunologic
/ metabolism
Female
Middle Aged
Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Receptors, Tumor Necrosis Factor, Member 14
/ metabolism
Immune Checkpoint Inhibitors
/ therapeutic use
Adult
Treatment Outcome
CD8-Positive T-Lymphocytes
/ immunology
Advanced melanoma
HVEM
T cell polyfunctionality
anti-PD1
biomarkers of response
blood immuno-monitoring
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2024
2024
Historique:
medline:
28
6
2024
pubmed:
28
6
2024
entrez:
28
6
2024
Statut:
epublish
Résumé
The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.
Identifiants
pubmed: 38939518
doi: 10.1080/2162402X.2024.2372118
pii: 2372118
pmc: PMC11210932
doi:
Substances chimiques
Receptors, Immunologic
0
BTLA protein, human
0
Programmed Cell Death 1 Receptor
0
Receptors, Tumor Necrosis Factor, Member 14
0
Immune Checkpoint Inhibitors
0
TNFRSF14 protein, human
0
PDCD1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2372118Informations de copyright
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
SD received institutional research grants from MSD, BMS and Pierre Fabre companies.