Evidence map›Paper›PMID 40952384›Full record

ArticleCancer research communications2025

Immune Activation Signatures Associated with Fatigue in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy.

Howard L Li, Soren Charmsaz, Mari Nakazawa, Stephanie L Alden, Madelena Brancati, James M Leatherman, Ervin Griffin, Hua-Ling Tsai, Nicole E Gross, Christopher J Thoburn and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Observational
  3. Article
  4. Article
  5. Review
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

30 authors.

Howard L LiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-2223-5444
Soren CharmsazSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-9148-9870
Mari NakazawaSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-6055-8960
Stephanie L AldenSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-0500-8696
Madelena BrancatiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0009-0009-2401-3694
James M LeathermanSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-1721-2128
Ervin GriffinSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0009-0004-7368-1561
Hua-Ling TsaiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-8388-6297
Nicole E GrossSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-8936-207X
Christopher J ThoburnSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-7743-9183
Alexei HernandezSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-6044-2631
Erin M CoyneSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-0393-6600
Sarah M ShinSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-7658-5899
Royce P LeeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0009-0008-7771-3208
Evan J LipsonSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-2976-0911
Burles A JohnsonSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-7180-8790
Aliyah PabaniSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0009-0006-7605-8497
Yasser GedSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-6671-7002
Marina BarettiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-0125-2405
Julie R BrahmerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-2443-8395
Jean Hoffman-CensitsSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-6970-6509
Tanguy Y SeiwertSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-7919-8272
Daniel J ZabranskySidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0002-8184-3346
Jennifer N DurhamSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0001-9097-9125
Elizabeth M JaffeeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-3841-6549
G Scott ChandlerF. Hoffmann-La Roche Ltd., a member of the imCORE network, Basel, Switzerland.ORCID 0000-0001-5339-9906
Brittany L AdlerDivision of Rheumatology, Johns Hopkins University, Baltimore, Maryland.ORCID 0000-0001-9912-2435
Won Jin HoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-2644-5086
Chester KaoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-2568-2071
Mark YarchoanSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.ORCID 0000-0003-4401-0748

Funding

Genentech (Genentech USA) 137515
6 · The paper itself

Abstract

Fatigue is a common and often debilitating adverse event among patients receiving immune checkpoint inhibitor (ICI) therapy, yet its underlying immunologic mechanisms remain poorly defined. We prospectively collected clinical data and blood samples from patients with solid tumors receiving ICI therapy. Patients were prospectively surveyed at month 2, 4, or 6 on treatment to assess for the presence and severity of fatigue as compared with treatment baseline. We analyzed peripheral lymphocyte populations by cytometry by time of flight and peripheral levels of 39 cytokines with a Luminex multiplex assay to identify dynamic immune changes associated with ICI-related fatigue. Of 53 patients enrolled, 31 (58.5%) reported worsening fatigue during ICI therapy. Patients reporting fatigue exhibited broad early-treatment elevations in circulating cytokines, with the most prominent increases observed in the Th1-associated cytokine cluster, including IFN-γ, IL-2, and IL-12. In parallel, several clusters of cytotoxic effector CD8+ T cells expanded significantly from baseline in the fatigued group. Fatigue was not associated with objective tumor response or with the development of other clinically meaningful immune-related adverse events. In a pan-tumor cohort treated with ICIs, increases in clusters of cytotoxic effector CD8+ T cells in parallel with related Th1-associated cytokines were associated with ICI-related fatigue, implicating fatigue as a potential marker of immune activation in this population. SIGNIFICANCE: This study illuminates dynamic changes in peripheral cytokines and immune cell clusters that are associated with ICI-related fatigue. Namely, this study implicates the Th1 pathway as a novel contributor to ICI-related fatigue and identifies ICI-related fatigue as a clinical surrogate for immune activation in patients receiving ICI therapy. Recognizing that fatigue may be a biomarker of heightened immune activity influences monitoring strategies and informs supportive care interventions during immunotherapy.

Indexed as

FatigueImmune Checkpoint InhibitorsNeoplasmsAdultAgedAged, 80 and overCD8-Positive T-LymphocytesCytokinesFemaleHumansMaleMiddle AgedProspective StudiesCytokinesImmune Checkpoint Inhibitors

Identifiers

PMID40952384
PMCPMC12485599

What Socratic holds

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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.