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Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue
Published on: May 17, 2018
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Immune Activation Signatures Associated with Fatigue in Cancer Patients Undergoing Immune Checkpoint Inhibitor
Howard L Li1,2, Soren Charmsaz1,2, Mari Nakazawa1,2
1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland.
Cancer Research Communications
|September 15, 2025
Summary
Immune checkpoint inhibitor (ICI) therapy can cause fatigue by activating T cells and increasing Th1 cytokines. This fatigue may signal heightened immune activity in patients with solid tumors.
Area of Science:
- Immunology
- Oncology
- Clinical Medicine
Background:
- Fatigue is a frequent adverse event in immune checkpoint inhibitor (ICI) therapy.
- The immunological mechanisms driving ICI-related fatigue are not well understood.
Purpose of the Study:
- To investigate the dynamic immune changes associated with fatigue in patients undergoing ICI therapy.
- To identify potential biomarkers for ICI-related fatigue.
Main Methods:
- Prospective collection of clinical data and blood samples from patients with solid tumors receiving ICI therapy.
- Assessment of fatigue severity at 2, 4, or 6 months of treatment.
- Analysis of peripheral lymphocyte populations using cytometry by time of flight.
- Quantification of 39 cytokines using a Luminex multiplex assay.
Main Results:
- Over half of patients (58.5%) reported worsening fatigue during ICI therapy.
- Fatigued patients showed elevated circulating cytokines, particularly Th1-associated cytokines (IFN-γ, IL-2, IL-12).
- Expansion of cytotoxic effector CD8+ T cells was observed in fatigued patients.
- Fatigue was not linked to tumor response or other immune-related adverse events.
Conclusions:
- Increased cytotoxic effector CD8+ T cells and Th1 cytokines are associated with ICI-related fatigue.
- ICI-related fatigue may serve as a clinical surrogate for immune activation.
- Fatigue can inform monitoring and supportive care strategies in immunotherapy patients.
