Serum levels of the interleukin-6 family cytokine leukemia inhibitory factor (LIF) are higher in patients who did not respond to radiation therapy, according to new research. LIF levels were found to be predictive of response to radiation therapy in patients with nasopharyngeal carcinoma (NPC).
NPC affects the cells lining the nasopharynx. The annual incidence rate of NPC is about 25-fold higher in Southeast Asia than in the Western world. Although the majority of cases can be cured by radiation therapy, 20% are resistant to radiation treatment. Radioresistance is a major cause of treatment failure in many cases.
Yu-Sun Chang, PhD, and colleagues at Chang Gung University in Taoyuan, Taiwan, sought to find a way to predict which individual cases of NPC would be sensitive to radiation therapy. They explained that, although inflammatory cytokines play a pivotal role in modulating tumor responses to irradiation, few cytokines have been validated as reliable markers in predicting radiosensitivity. They evaluated cytokines in serum samples from 71 patients with NPC and 28 healthy individuals. Their research was published in The Journal of Clinical Investigation (2013; doi:10.1172/JCI63428).
The levels of LIF were higher in serum samples from NPC patients who developed local recurrence after treatment than in samples from those in complete tumor remission. Poorer local recurrence-free survival was correlated with higher LIF levels.
Tests in cell lines and in a mouse model of NPC found that LIF-mediated effects were decreased by the use of a soluble antagonist of LIF or by rapamycin, which is a mammalian target of rapamycin (mTOR) inhibitor. The protein mTOR has roles in regulating cell growth and proliferation, along with motility and survival. When the LIF-mediated effects were decreased, growth was arrested and sensitivity to radiation increased.
The authors suggested that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients. They stated that their results indicate that, “LIF might be a valuable biomarker for predicting tumor radiosensitivity and suggest that inhibiting the interactions between LIF and downstream targets, such as with a LIF antagonist, could be an attractive approach for sensitizing the radioresistant NPC tumor cells.”