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- Title
Immune System Disorder and Cancer-Associated Cachexia.
- Authors
Zhang, Lingbing; Bonomi, Philip D.
- Abstract
Simple Summary: Cancer-associated cachexia (CAC) is a serious condition wherein people with cancer lose muscle and fat, even with proper nutrition. It leads to weakness and can make treatment less effective. This review looks at how the body's immune system and certain proteins affect CAC. Studies show that specific proteins, like IL-6 and TNF-α, play a crucial role in causing muscle and fat loss. Other cells in the immune system, called MDSCs, make CAC worse by causing inflammation. Clinical studies also found high levels of certain proteins in people with CAC. Understanding these processes might improve treatments, especially for those undergoing immunotherapy. A new drug called R-ketorolac has shown promise in reversing weight loss in animals. Combining drugs like this with immunotherapy could help patients with cancer suffering from CAC. However, more research is needed to fully understand how immune problems and CAC interact during treatment. Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.
- Subjects
RISK assessment; PROTEINS; NEUTROPHIL lymphocyte ratio; IMMUNOTHERAPY; MYELOID-derived suppressor cells; KETOROLAC; TUMORS; CACHEXIA; INFLAMMATION; CYTOKINES; MUSCULAR atrophy; IMMUNOLOGIC diseases; TUMOR necrosis factors; INTERLEUKINS; DISEASE risk factors; DISEASE complications
- Publication
Cancers, 2024, Vol 16, Issue 9, p1709
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16091709