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Cytokine Levels in Plasma and PHA Activated T Cells in Head and Neck Cancer Patients

Nikhit Kambdur, Ankita Umrao, Gururaj A Rao and Jyothsna A Rao

Cytokines play a pivotal role in cancer, as these act as mediators in response to several physiological factors, caused by disease burden or interventions like surgery, chemotherapy and radiation. The levels of these cytokines can also act as biomarkers, and help in predicting a relapse episode or by analysing the efficacy of an intervention. Combination approaches based on the Cellular Immunotherapy are now being considered to reset the immune system thereby help achieve better prognosis in cancer treatment. One such approach is Autologous Activated T Cells Therapy (ATC), which entails in vitro activation of patient's own T cells from the peripheral blood and infusion of these activated T cells back into the patient. This helps in resetting the immune system which makes it conducive for better antigen presentation and a TH1 mediated anti-tumour response.

Since there is an immuno-suppressive milieu pre-existing in the body, it is important to check if the Autologous activation of T cells produces immunosuppressive cytokines, which would then undermine the intent of this approach.

In this study, we have measured the cytokines level in plasma and PHA stimulated mononuclear cells in control healthy population and head and neck cancer patients. Interleukin 10 (IL 10) and Transforming growth factor-beta (TGFβ) which fall under the anti-inflammatory category (pro-tumour) and Interferon-gamma (IFNγ) and Tumour necrosis factor-alpha (TNFα) which fall under the category of pro-inflammatory (anti-tumor) have been studied by ELISA.

Results show a significant decrease in plasma TGFβ levels in patients when compared to healthy controls. There is no increase in TGFβ levels on PHA stimulation, which is comparable to the healthy controls. There is an increase in plasma IL 10 levels in patients as compared to controls, indicating slight immunosuppression, although no significant increase in IL 10 is observed on PHA stimulation. There is a slight increase in plasma TNFα levels in patient population. On PHA stimulation, patient T cells produce significantly less TNFα when compared to control. There is a slight elevation in plasma IFNγ levels in patients, while on PHA stimulation; patient T cells produce comparable amounts of IFNγ, when compared to control.

These results indicate a) that Autologous Activated T Cell (ATC) does not result in amplification of TGFβ, and IL10 cytokines, b) Patients have the ability to produce IFNγ on PHA stimulation, indicating a functional immune system, c) PHA stimulation in patient results in less TNFα when compared to control, indicating a compromise in the T cell compartment.