Targeted Immunomodulation for Alleviating Cancer-related Fatigue in Lung Cancer Patients: Unraveling the Multifaceted Role of Brain-immune Interactions
Shivangi Jha1, Ashvath Pillai2, Sai Kumar Reddy Pasya3, Vansh Varma4, Cyrus Yadav5, Vaibhav Sanjay Nasre5, Naveen Goyal6, Gaurish Angawalkar7, Siddharth Prabhakar7
1Webster Center for Quality and Safety, Massachusetts General Hospital, Harvard Medical School, 2SSPM Medical College and Lifetime Hospital, Padve, Sindhudurg, India, 3University of Kansas Medical Center, 4GMERS Medical College and Lifetime Hospital Valsad, Gujarat, 5Kazan state medical university, Kazan, Russia, 6Government Medical College, Patiala, PunjabGovernment Medical College, Patiala, Punjab, 7SSPM Medical College and Lifetime Hospital, Padve, Sindhudurg
Objective:
Cancer-related fatigue (CRF) is a serious side effect that affects a large number of lung cancer patients receiving chemotherapy. Immune checkpoint inhibitors (ICIs), have shown potential in enhancing survival and are immunomodulatory in their therapy.
Background:
This review aims to assess the efficacy of immunomodulatory therapy for CRF in lung cancer patients based on prognosis and neurocognitive function as well as the role of brain–immune interactions.
Design/Methods:
A systematic search was performed in PubMed, Embase, and Scopus. The inclusion criteria were age greater than 18 years, diagnosed with lung cancer at any stage, and receiving immunomodulatory agents with assessment of CRF. The exclusion criteria consisted of animal studies, reviews, and studies not focusing on CRF in lung cancer. Six reviewers worked independently to screen articles and assessed for eligibility. Data extraction involved details of the studies, patients, immune-related biomarkers, CRF manifestations, and treatment complications. Study quality was assessed using the Cochrane Risk of Bias Tool and Newcastle-Ottawa Scale, with evidence certainty evaluated through the GRADE framework.
Results:
Sixteen studies were included. Immune checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab) generally improved progression-free and overall survival compared with chemotherapy. They also lowered neuroinflammatory markers (IL-6, TNF-α), suggesting a biological link to fatigue relief. However, responses were mixed — some studies showed no benefit on cancer-related fatigue, and a few even reported worsening fatigue in certain patients. Common immune-related side effects included pneumonitis, dermatitis, and liver toxicity. Quality-of-life results spread from clear fatigue improvement to minimal change.
Conclusions:
Immune checkpoint inhibitors while not only improving survival and brain function, likely by reducing inflammation, could help ease cancer-related fatigue in people with lung cancer . Still, everyone responds differently. Future research needs to predict who will benefit and ways to personalize treatment to avoid worsening of fatigue.
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