IL-6 promotes tumor growth through immune evasion but is dispensable for cachexia

Cancer cachexia, a debilitating syndrome characterized by systemic wasting in cancer patients, has long confounded researchers seeking to identify its underlying mechanisms. A recent study published in EMBO Reports sheds new light on this complex syndrome by challenging the conventional wisdom surrounding two widely accepted cachectic factors: interleukin-6 (IL-6) and leukemia inhibitory factor (LIF).

Depleting the cachectic factor IL-6 from tumors increases tumor immune infiltration and slows down tumor growth, but it does not prevent cachexia although circulating IL-6 is not elevated.

Researchers have long sought to identify mediators of cancer cachexia, proposing numerous cachectic factors over the years. However, targeting these factors has yet to yield an effective treatment, prompting a reevaluation of their biological roles.

Led by postdoctoral fellow Young-Yon Kwon and Dr. Sheng Hui, the study focused on the colon 26 carcinoma (C26) model, a well-established model for investigating cancer cachexia. Utilizing CRISPR technology to knock out the IL-6 gene in C26 cells, the researchers observed that while IL-6 knockout slowed tumor growth, cachexia still occurred, indicating that elevated circulating IL-6 is not necessary for cachexia development in this model. Furthermore, the study also investigated the role of LIF and found that it was not necessary for inducing cachexia in the C26 model.

These findings underscore the complexity of cancer cachexia and highlight the need for a more nuanced understanding of the factors driving this syndrome. The study also highlights the importance of closely monitoring tumor growth when assessing the role of potential cachectic factors. By demonstrating that inhibiting IL-6 slowed tumor growth in the C26 model, the study challenges the assumption that factors affecting tumor growth necessarily contribute to cachexia.

These findings open up new avenues for research into the underlying mechanisms of cancer cachexia. By challenging established beliefs, the study paves the way for more effective interventions for patients suffering from this debilitating syndrome.