Evidence map›Paper›PMID 39403935›Full record

Observational studyThe Journal of clinical investigation2024

Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures.

Chester J Kao, Soren Charmsaz, Stephanie L Alden, Madelena Brancati, Howard L Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman and 33 more

Erratum issuedAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Immune Checkpoint Inhibitor-Associated Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. High-Grade Immune-Related Adverse Events Resulting from Immune Checkpoint Inhibitor Treatment: Evaluation of Diagnostics and Outcomes in Admitted Patients.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Cutaneous adverse effects of combination epidermal growth factor receptor inhibitor and immune checkpoint inhibitor cancer therapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
    Article
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors.

Chester J KaoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Soren CharmsazSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Stephanie L AldenJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Madelena BrancatiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Howard L LiJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Aanika BalajiJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kabeer MunjalSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Kathryn HoweSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Sarah MitchellSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
James LeathermanSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Ervin GriffinSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Mari NakazawaSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Hua-Ling TsaiJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ludmila DanilovaJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chris ThoburnJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jennifer GizziJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nicole E GrossSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Alexei HernandezSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Erin M CoyneSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Sarah M ShinSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Jayalaxmi Suresh BabuSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
George W ApostolSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Jennifer DurhamSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Brian J ChristmasSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Maximilian F KonigDivision of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Evan J LipsonSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Jarushka NaidooSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Laura C CappelliDivision of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Aliyah PabaniSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Yasser GedSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Marina BarettiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Julie BrahmerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Jean Hoffman-CensitsSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Tanguy Y SeiwertSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Rachel Garonce-HedigerF. Hoffmann-La Roche Ltd., a member of the imCORE network, Basel, Switzerland.
Aditi GuhaGenentech Inc., a member of the imCORE network, South San Francisco, California, USA.
Sanjay BansalGenentech Inc., a member of the imCORE network, South San Francisco, California, USA.
Laura TangGenentech Inc., a member of the imCORE network, South San Francisco, California, USA.
Elizabeth M JaffeeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
G Scott ChandlerF. Hoffmann-La Roche Ltd., a member of the imCORE network, Basel, Switzerland.
Rajat MohindraF. Hoffmann-La Roche Ltd., a member of the imCORE network, Basel, Switzerland.
Won Jin HoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
Mark YarchoanSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI THOMPSON, ELIZABETH D · 1993 to 2022
$54.6M
Comprehensive Analysis and Multi-Omics Data Integration for Cancer-Related StudiesR50CA243627 · NCI · JOHNS HOPKINS UNIVERSITY · PI Ludmila Danilova · 2019 to 2026
$975k
Understanding Inflammatory Arthritis due to Immune Checkpoint InhibitorsK23AR075872 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CAPPELLI, LAURA CHRISTINE · 2019 to 2023
$779k
Mass Cytometer CyTOF XT for Single-Cell BiologyS10OD034407 · OD · JOHNS HOPKINS UNIVERSITY · PI HO, WON JIN · 2024 to 2024
$499k
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA062924NCI NIH HHS R50 CA243627NIAMS NIH HHS K23 AR075872NIH HHS S10 OD034407
6 · The paper itself

Abstract

BACKGROUNDImmune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pan-tumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies.METHODSIn an observational study, we prospectively collected blood samples and performed regular clinical evaluations for irAEs in patients receiving ICI therapy as standard of care for solid tumors. We performed in-parallel analysis of cytokines by Luminex immunoassay and circulating immune cells by cytometry by time-of-flight (CyTOF) at baseline and on treatment to investigate mechanisms of irAEs.RESULTSWe enrolled 111 patients, of whom 40.5% developed a symptomatic irAE (grade ≥ 2). Development of a grade ≥ 2 irAE was positively associated with the use of combination ICI and a history of an autoimmune disorder. Early changes in T helper 17 (Th17) (IL-6, IL-17f), type 2 (IL-5, IL-13, IL-25), and type 1 (TNF-α) cytokine signatures and congruent on-treatment expansions of Th17 and Th2 effector memory (Th2EM) T cell populations in peripheral blood were positively associated with the development of grade ≥2 irAEs. IL-6 levels were also associated with inferior cancer-specific survival and overall survival.CONCLUSIONSIn a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early ICI treatment was associated with the development of clinically relevant irAEs but not antitumor responses, providing possible targets for monitoring and therapeutic interventions.FUNDINGJohns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, the NCI SPORE in Gastrointestinal Cancers (P50 CA062924), NCI grant (R50CA243627 to LD), the NIH Center Core Grant (P30 CA006973), Swim Across America (to MY), NIAMS (K23AR075872 to LC), and imCORE-Genentech grant 137515 (to Johns Hopkins Medicine on behalf of MY).

Indexed as

NeoplasmsTh17 CellsTh2 CellsAdultAgedAged, 80 and overFemaleHumansImmune Checkpoint InhibitorsImmunotherapyMaleMiddle AgedProspective StudiesImmune Checkpoint InhibitorsCytokinesImmunotherapyOncologyT cells

Identifiers

PMID39403935
PMCPMC11473156

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.