Evidence map›Paper›PMID 38280067›Full record

ArticleCancer immunology, immunotherapy : CII2024

Activation of cytotoxic lymphocytes through CD6 enhances killing of cancer cells.

Mikel Gurrea-Rubio, Qi Wu, M Asif Amin, Pei-Suen Tsou, Phillip L Campbell, Camila I Amarista, Yuzo Ikari, William D Brodie, Megan N Mattichak, Sei Muraoka and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 1 country.

Mikel Gurrea-RubioDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Qi WuDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
M Asif AminDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Pei-Suen TsouDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Phillip L CampbellDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Camila I AmaristaDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Yuzo IkariDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
William D BrodieDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Megan N MattichakDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Sei MuraokaDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Peggy M RandonDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Matthew E LindDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Jeffrey H RuthDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Yang Mao-DraayerDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Shengli DingXilis, Inc., Durham, NC, USA.
Xiling ShenXilis, Inc., Durham, NC, USA.
Laura A CooneyDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA.
Feng LinDepartment of Immunity and Inflammation, Lerner Research Institute, Cleveland, OH, USA.
David A FoxDepartment of Internal Medicine, Division of Rheumatology, University of Michigan and Autoimmunity Center of Excellence, Ann Arbor, MI, USA. dfox@med.umich.edu.
University of Michigan · USCleveland Clinic Lerner College of Medicine · US

Funding

TRAINING OF ARTHRITIS RESEARCH SCIENTISTST32AR007080 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason Knight · 1986 to 2026
$6.3M
University of Michigan Clinical Autoimmunity Center of ExcellenceUM1AI144298 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN, KHANNA, DINESH · 2019 to 2023
$546k
Immunotherapy of prostate cancer using an anti-CD6 monoclonal antibodyR21CA287325 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN · 2024 to 2025
$401k
NCI NIH HHS R21 CA287325NIAID NIH HHS UM1 AI144298NIAMS NIH HHS T32 AR007080
6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICIs) have demonstrated efficacy and improved survival in a growing number of cancers. Despite their success, ICIs are associated with immune-related adverse events that can interfere with their use. Therefore, safer approaches are needed. CD6, expressed by T-lymphocytes and human NK cells, engages in cell-cell interactions by binding to its ligands CD166 (ALCAM) and CD318 (CDCP1). CD6 is a target protein for regulating immune responses and is required for the development of several mouse models of autoimmunity. Interestingly, CD6 is exclusively expressed on immune cells while CD318 is strongly expressed on most cancers. Here we demonstrate that disrupting the CD6-CD318 axis with UMCD6, an anti-CD6 monoclonal antibody, prolongs survival of mice in xenograft mouse models of human breast and prostate cancer, treated with infusions of human lymphocytes. Analysis of tumor-infiltrating immune cells showed that augmentation of lymphocyte cytotoxicity by UMCD6 is due to effects of this antibody on NK, NKT and CD8 + T cells. In particular, tumor-infiltrating cytotoxic lymphocytes from UMCD6-treated mice expressed higher levels of perforin and were found in higher proportions than those from IgG-treated mice. Moreover, RNA-seq analysis of human NK-92 cells treated with UMCD6 revealed that UMCD6 up-regulates the NKG2D-DAP10 receptor complex, important in NK cell activation, as well as its downstream target PI3K. Our results now describe the phenotypic changes that occur on immune cells upon treatment with UMCD6 and further confirm that the CD6-CD318 axis can regulate the activation state of cytotoxic lymphocytes and their positioning within the tumor microenvironment.

Indexed as

Antineoplastic AgentsNeoplasmsAnimalsAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, NeoplasmCell Adhesion MoleculesHumansLymphocytesMiceTumor MicroenvironmentAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, T-LymphocyteAntigens, NeoplasmAntineoplastic AgentsCD6 antigenCDCP1 protein, humanCell Adhesion MoleculesCD6Cytotoxic lymphocyteImmunotherapyNK

Identifiers

PMID38280067
PMCPMC10821976
OpenAlexW4391278269

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.