Evidence map›Paper›PMID 36725085›Full record

ArticleJournal for immunotherapy of cancer2023

Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity.

Mark Sorin, Elham Karimi, Morteza Rezanejad, Miranda W Yu, Lysanne Desharnais, Sheri A C McDowell, Samuel Doré, Azadeh Arabzadeh, Valerie Breton, Benoit Fiset and 10 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 60 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 1 country.

Mark Sorin *Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Elham Karimi *Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Morteza RezanejadDepartment of Psychology and Computer Science, University of Toronto, Toronto, Ontario, Canada.
Miranda W YuRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Lysanne DesharnaisRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Sheri A C McDowellRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Samuel DoréRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Azadeh ArabzadehRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Valerie BretonRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Benoit FisetRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.ORCID 0000-0003-0372-8868
Yuhong WeiRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Roni RayesRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Michele OrainInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, Canada.
Francois CoulombeInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, Canada.
Venkata S K ManemInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, Canada.
Andreanne GagneInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, Canada.
Daniela F QuailRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.
Philippe JoubertInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, Canada.
Jonathan D SpicerRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada logan.walsh@mcgill.ca jonathan.spicer@mcgill.ca.
Logan A WalshRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada logan.walsh@mcgill.ca jonathan.spicer@mcgill.ca.ORCID 0000-0001-8771-2577
McGill University · CAInstitut universitaire de cardiologie et de pneumologie de Québec · CAUniversity of Toronto · CA

Funding

CIHR PJT-162137
6 · The paper itself

Abstract

backgroundImmunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI.

methodsHere, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade.

resultsWe resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes. DISCUSSION: Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAnimalsChemokine CXCL13HumansImmune Checkpoint InhibitorsImmunotherapyMiceTumor MicroenvironmentChemokine CXCL13CXCL13 protein, humanCxcl13 protein, mouseImmune Checkpoint InhibitorsCytokinesImmunotherapyLung Neoplasms

Identifiers

PMID36725085
PMCPMC9896310
OpenAlexW4318826747

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.