Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer.

B cells Immunotherapy Kassandra Machine learning NK cells RNA Sequencing T cells blood test cancer cancer patients cell-typing classifier flow cytometry immune cells immune checkpoint blockade immune status immune system immunoprofiling immunotherapy biomarker immunotype immunotype signature scores immunotype signatures monocytes peripheral blood systems immunology tumor microenvironment

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
13 May 2024
Historique:
received: 31 08 2023
revised: 20 02 2024
accepted: 15 04 2024
medline: 15 5 2024
pubmed: 15 5 2024
entrez: 14 5 2024
Statut: ppublish

Résumé

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.

Identifiants

pubmed: 38744245
pii: S1535-6108(24)00132-6
doi: 10.1016/j.ccell.2024.04.008
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

759-779.e12

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests This research was funded by BostonGene, Corp. N.F. is the Chief Medical Officer of BostonGene, Corp., and all authors affiliated with BostonGene, Corp. were employees thereof at the time the study was performed. M.F.G., A.Bagaev, D.D., A.Z., B.S., E.T., P.T., and A.A.S. are inventors on patents related to this work.

Auteurs

Daniiar Dyikanov (D)

BostonGene, Corp., Waltham, MA, USA.

Aleksandr Zaitsev (A)

BostonGene, Corp., Waltham, MA, USA.

Tatiana Vasileva (T)

BostonGene, Corp., Waltham, MA, USA.

Iris Wang (I)

BostonGene, Corp., Waltham, MA, USA.

Arseniy A Sokolov (AA)

BostonGene, Corp., Waltham, MA, USA.

Evgenii S Bolshakov (ES)

BostonGene, Corp., Waltham, MA, USA.

Alena Frank (A)

BostonGene, Corp., Waltham, MA, USA.

Polina Turova (P)

BostonGene, Corp., Waltham, MA, USA.

Olga Golubeva (O)

BostonGene, Corp., Waltham, MA, USA.

Anna Gantseva (A)

BostonGene, Corp., Waltham, MA, USA.

Anna Kamysheva (A)

BostonGene, Corp., Waltham, MA, USA.

Polina Shpudeiko (P)

BostonGene, Corp., Waltham, MA, USA.

Ilya Krauz (I)

BostonGene, Corp., Waltham, MA, USA.

Mary Abdou (M)

BostonGene, Corp., Waltham, MA, USA.

Madison Chasse (M)

BostonGene, Corp., Waltham, MA, USA.

Tori Conroy (T)

BostonGene, Corp., Waltham, MA, USA.

Nicholas R Merriam (NR)

BostonGene, Corp., Waltham, MA, USA.

Julia E Alesse (JE)

BostonGene, Corp., Waltham, MA, USA.

Noel English (N)

BostonGene, Corp., Waltham, MA, USA.

Boris Shpak (B)

BostonGene, Corp., Waltham, MA, USA.

Anna Shchetsova (A)

BostonGene, Corp., Waltham, MA, USA.

Evgenii Tikhonov (E)

BostonGene, Corp., Waltham, MA, USA.

Ivan Filatov (I)

BostonGene, Corp., Waltham, MA, USA.

Anastasia Radko (A)

BostonGene, Corp., Waltham, MA, USA.

Anastasiia Bolshakova (A)

BostonGene, Corp., Waltham, MA, USA.

Anastasia Kachalova (A)

BostonGene, Corp., Waltham, MA, USA.

Nika Lugovykh (N)

BostonGene, Corp., Waltham, MA, USA.

Andrey Bulahov (A)

BostonGene, Corp., Waltham, MA, USA.

Anastasiia Kilina (A)

BostonGene, Corp., Waltham, MA, USA.

Syimyk Asanbekov (S)

BostonGene, Corp., Waltham, MA, USA.

Irina Zheleznyak (I)

BostonGene, Corp., Waltham, MA, USA.

Pavel Skoptsov (P)

BostonGene, Corp., Waltham, MA, USA.

Evgenia Alekseeva (E)

BostonGene, Corp., Waltham, MA, USA.

Jennifer M Johnson (JM)

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA.

Joseph M Curry (JM)

Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Alban J Linnenbach (AJ)

Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Andrew P South (AP)

Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.

EnJun Yang (E)

The Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.

Kirill Morozov (K)

BostonGene, Corp., Waltham, MA, USA.

Anastasiya Terenteva (A)

BostonGene, Corp., Waltham, MA, USA.

Lira Nigmatullina (L)

BostonGene, Corp., Waltham, MA, USA.

Dmitry Fastovetz (D)

BostonGene, Corp., Waltham, MA, USA.

Anatoly Bobe (A)

BostonGene, Corp., Waltham, MA, USA.

Linda Balabanian (L)

BostonGene, Corp., Waltham, MA, USA.

Krystle Nomie (K)

BostonGene, Corp., Waltham, MA, USA.

Sheila T Yong (ST)

BostonGene, Corp., Waltham, MA, USA.

Christopher J H Davitt (CJH)

BostonGene, Corp., Waltham, MA, USA.

Alexander Ryabykh (A)

BostonGene, Corp., Waltham, MA, USA.

Olga Kudryashova (O)

BostonGene, Corp., Waltham, MA, USA.

Cagdas Tazearslan (C)

BostonGene, Corp., Waltham, MA, USA.

Alexander Bagaev (A)

BostonGene, Corp., Waltham, MA, USA.

Nathan Fowler (N)

BostonGene, Corp., Waltham, MA, USA.

Adam J Luginbuhl (AJ)

Department of Otolaryngology Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Ravshan I Ataullakhanov (RI)

BostonGene, Corp., Waltham, MA, USA.

Michael F Goldberg (MF)

BostonGene, Corp., Waltham, MA, USA. Electronic address: michael.goldberg@bostongene.com.

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Classifications MeSH